Echoscopes have revolutionized the discovery and maintenance of offshore renewable wind farms. In the construction process of installing huge underwater turbine base structures, huge amounts of silt clouds obstruct vision and prevent video cameras as well as one-beam sonar technology from doing its job. However, by using the real-time 3D images produced by the Echoscope, the engineers managed to view the exact process of how these huge jacket structures were settling at the bottom of the sea, observing unknown scouring patterns and instabilities before the anchoring process began.

Echoscope is also the name of an alternative segment of the weekly articles. In this series, SPLICED will feature interviews with researchers, professionals and scientists from a plethora of diverse biological backgrounds with unique and truly insightful stories to tell. The signature type of publications will all the same continue.

Antibodies and Antigens

An antigen is a special molecule that resides on the surface of these foreign entities such as viruses and bacteria. Once your body senses these molecules of foreign bodies, there are some cells in your body that start producing specially tailored molecules known as antibodies. In the same way, once an antibody finds its target antigen, it would block the invasion process of the antigen.

Dr. Madhuri Manohar

Specialising her research on antibodies, scientist is also a creator on Substack writing for her very own publication The Binding Site to help learners and other scholars design and perform experiments more efficiently.

below is the interview in a [question + answer from the scientist] format:

1. If you had to explain your current research using only objects in a kitchen, how would you do it?

My work focuses on engineering antibodies to target specific antigens. You can think of an antigen as a specific protein we want to study or target, and an antibody as the customized tool designed to interact with it. If I had to explain my job using a kitchen, I basically "engineer the perfect fork." Imagine a bowl full of different fruits and ingredients. We want to design a specialized fork that picks up only the exact piece of fruit we're after, grabbing it seamlessly and holding on tightly, without snagging any of the other ingredients in the bowl.

2. What is one problem your work could potentially solve in 10 years?

Antibodies are incredible tools with endless applications. Vaccines rely on them as a line of defense, diagnostic tests use them to detect diseases, and modern therapeutics use them to deliver highly targeted cancer treatments. A challenge I am particularly passionate about tackling over the next decade is Antimicrobial Resistance (AMR). As our existing antibiotics become increasingly ineffective against common bacterial infections, researchers are exploring how engineered antibodies could step in as a targeted alternative to combat resistant superbugs.

3. Is there a moment in your research where you completely failed, and what did that failure actually teach you?

Oh, absolutely! I believe that in science, failure is really just refinement. There’s a famous story about Thomas Edison trying hundreds of designs before mastering the lightbulb. He didn't look at those early attempts as total losses, but as necessary steps toward the right solution. Failure teaches you far more than instant success ever can.

One major lesson I’ve learned is the power of owning your failures openly. Admitting when something didn't work immediately makes you relatable to others. That honesty creates room for mentors and colleagues to step in, share their experience, and guide you forward. You end up emerging from the setback with far more knowledge than if you had tried to hide it. It’s never a lost cause.

4. If you were 16 again, what is one biology-related skill you would start learning today?

More than a specific lab technique, the mind-set I wish I had cultivated earlier is genuine, active curiosity. Louis Pasteur famously said, "In the fields of observation, chance favors only the prepared mind." If I had approached science back then with the fascination I have for it now, I think I would have become a strong scientist much sooner. At 16, I was mostly focused on memorizing biological terms the night before an exam. I wish I had spent less time cramming and more time simply appreciating the wonder and complexity of how living systems work.

Takeaways

Biology is so much more than merely understanding the mechanisms and processes that sustain life; there is still an abundance of unknowns that simply require to be looked at through a lens of wonder and appreciation.

Failures in science are almost never a real setback; by proving something wrong or finding out something does not work in the way expected, the results are more of a redirection than a dead-end. Owning your failures rather than dismissing them as ‘bad’ allows the progression of a learning curve and invites new possibilities.

Acknowledgements

Thank you to Dr. Madhuri Manohar for her insightful and honest answers.

Check out The Binding Site on Substack

INTRODUCTION

What if a future cure for cancer wasn’t from chemotherapy, immunotherapies, or surgery but something normally thought of as “bad”? Bacteria (yes, really) could offer us a solution to normally hard-to-reach tumors that our current attempts haven’t been able to crack, through a process most people associate with computers and machines. Using programming languages, scientists have been able to make bacteria detect and fight cancer using their naturally existing machinery.

In this blog post, we’ll cover the fascinating field behind this discovery, synthetic biology, why bacteria are actually a smart choice for the fight against cancer, how scientists code bacteria, discoveries scientists have made to use bacteria for cancer, and the challenges behind this field.

WHAT IS SYNTHETIC BIOLOGY

Synthetic biology today has developed far more than what was expected from it ten years ago. Cells are being re-engineered to solve problems like sustainability, targeted therapy, customizable medicine, and so much more.

The field itself can be seen as a transition from viewing nature as a finished piece of art to viewing nature as a living toolbox with genes as the language of instructions. Instead of analyzing the instruction manual as it stands, scientists are now learning how to read the code written by DNA as if it were computer programming and using the knowledge gained to create new realities.

Picture microbes that can eliminate microplastics in the ocean without making any noise, plants that can glow at night so as to replace street lamps, or even cells that have been specially designed to find and correct diseases in the human body.

Using advancing genetic modification technologies, the capabilities of science and modern biology in altering genes and creating new ones have expanded the horizons of possibility.

WHY CODE BACTERIA

So, why do we choose to code bacteria instead of human or animal cells instead? This is due to the fact that bacteria are much simpler and duplicate much faster, while requiring fewer resources to stay alive.

Bacteria come from the Bacteria domain. The other 2 domains of life are Archaea and Eukarya. Their DNA is stored in the form of a small circular plasmid, which can be exchanged with other bacteria in a process called horizontal gene transfer. Think of the plasmid like the chromosomes in a eukaryotic cell. Bacteria have 1 main plasmid and other smaller plasmids from other bacteria. They contain a plasma membrane, cell wall, a capsule that keeps the cell from drying out, and appendages that allow them to stick onto surfaces.

Bacteria are much more simple that eukaryotic cells. They have less DNA, due to a higher selectivity for useful genes. Eukaryotic cells, on the other hand, can retain DNA that doesn’t provide value for a long time. Inserting new DNA is also much easier with bacteria. They are already naturally accustomed to swapping DNA with other bacteria, whereas eukaryotic cells have mechanisms to prevent interference with their DNA.

They duplicate much faster too, dividing every 20 minutes. Eukaryotic cells usually take 24 hours to divide. This is useful for making large batches for testing. Bacteria also require much less to survive.

Why are we specifically trying to use bacteria to fight cancer? Well, bacteria naturally grow inside of tumor cells. The environment around tumor cells is usually devoid of immune cells, allowing the bacteria to divide easily without resistance. We can insert genes that allow bacteria to detect or fight cancer, allowing us to reach places in the tumor that are traditionally very hard to access.

HOW TO CODE BACTERIA

Here, we’ll be covering the basics of how to program bacteria. If you’re interested in more advanced concepts, explore the links at the bottom of this post. Coding bacteria requires using plasmids and inserting them into a bacterium. We can insert DNA into the plasmid, which can come from other organisms or be synthesized by scientists via DNA synthesizer machines. A DNA synthesizer lets scientists make a custom DNA sequence from scratch with nucleotides.

Plasmids can be obtained from bacteria by using methods that open cells and separate the DNA from other components. Scientists can either use naturally occurring plasmids or plasmids engineered for research purposes. These plasmids are cut open by enzymes called restriction enzymes. These enzymes are derived from bacteria, and they cut open the plasmid, leaving sticky ends that have overhangs of DNA. These short overhangs form temporary hydrogen bonds between complementary sequences of bases on other DNA sections cut with the same restriction enzyme.

The newly opened plasmid and the desired DNA (cut with the same restriction enzyme) are mixed together. A small number of sticky ends from the DNA pair up together temporarily with the sticky ends of the plasmid. After this, DNA ligase stitches the two pieces of DNA together with a strong covalent bond to make a new recombinant plasmid.

After the DNA has been combined with the plasmid, the bacteria and plasmids are both placed into a solution containing lots of calcium ions, which neutralize the negativity of the plasmid DNA and bacterial cell membrane. The combination of the calcium ions and a procedure of cooling the mixture and then giving it a heat shock (which makes temporary openings in the membrane)  makes it more likely that the plasmid passes through the cell membrane into the bacteria. This process is called transformation. The process isn’t very efficient since only a small amount passes through.

How do scientists know that the plasmid is inside the bacteria? They usually insert another piece of DNA, like an antibiotic resistance gene, that lets them test the bacteria afterward. This piece of DNA is called a selectable marker. A popular way to test DNA involves inserting a reporter gene ( DNA attached to the promoter of a gene that only works when that gene is activated ) that makes GFP, or green fluorescent protein, which glows bright green under UV light.

HOW CODED BACTERIA FIGHT CANCER

Recent developments showcase a unique ability to design and optimize gene networks with extraordinary accuracy. Scientists have developed living bacterial systems that can deliver drugs directly to targeted environments, thus producing them in situ and avoiding any adverse effects caused by their administration in other parts of the body. At the same time, progress in research on cell-free synthetic systems and metabolic engineering allows one to produce valuable medicines, materials, and bio-plastics without the need for living organisms. In environmental biotechnology, scientists are developing circuits in plants and microbes to detect and remediate industrial pollutants, and recent developments in synthetic chloroplasts seek to increase the rate of carbon fixation in plants significantly.

In cancer research, scientists at the University of Waterloo earlier this year made bacteria that could engulf tumors from the inside. Tumors usually have an oxygen-poor core, and the scientists took advantage of this by using a soil bacterium that thrives in low-oxygen environments. They allowed it to grow inside the tumor, depleting nutrients from the tumor and eating it from the inside out. However, they ran into a problem.

The bacteria would start dying if they reached the oxygen-rich edges of the tumor mass. The scientists fixed this problem by using quorum sensing. Quorum sensing is a process where bacteria send chemical signals to each other to detect how dense their population is.

As the bacteria multiplied and their density grew inside the tumor, they released chemical signals. Once the population hit a specific density threshold, it triggered the activation of an oxygen resistance gene that the scientists placed.

CHALLENGES

There are still a lot of challenges with programming bacteria at the moment. The field is still young, which means that it’s constantly evolving. Some challenges include:

Not knowing the roles of certain genes and their widespread effects

We still don’t know what a large number of genes in bacteria do, and what their effect is on other genes once removed or modified. This can lead to unintended results and tedious trial-and-error testing to ensure experiments run smoothly.

Constructing genetic circuits

Constructing and inserting genetic circuits can be very tedious and labor-intensive. With a very small number of bacteria taking up modified plasmids, it can often take many attempts before a bacterium successfully expresses the desired result.

Testing bacteria for desired result

Testing how artificially engineered bacteria perform can take some time. Lots of different factors like growth and division rates, variability between different cells, and genetic circuit instability and unintended results can make trials last longer and stall innovation.

Ethical concerns

Bacteria could be synthesized for malicious purposes like producing toxic compounds or causing harm to patients. Labs might also unintentionally release toxic bacteria from experiments due to lax lab procedures.

Difficulty automating process

Swapping or adding new genetic material doesn’t always act predictably. Tuning genetic circuits still requires someone to tweak them to be optimized. Full automation and standardization are difficult at the moment.

Despite all of these challenges, the field has grown immensely from where it once started. In the future, we might be able to solve these challenges, leading to more innovative biologic solutions to the world’s problems.

RECENT INNOVATIONS IN SYN-BIO

Recent developments showcase a unique ability to design and optimize gene networks with extraordinary accuracy. Scientists have developed living bacterial systems that can deliver drugs directly to targeted environments, thus producing them in situ and avoiding any adverse effects caused by their administration in other parts of the body.

At the same time, progress in research on cell-free synthetic systems and metabolic engineering allows one to produce valuable medicines, materials, and bio-plastics without the need for living organisms. In environmental biotechnology, scientists are developing circuits in plants and microbes to detect and remediate industrial pollutants, and recent developments in synthetic chloroplasts seek to increase the rate of carbon fixation in plants significantly.

SUMMARY/ CONCLUSION

Synthetic biology is creating new ways to use bacteria as tools to fight cancer and other problems. Together with protein design platforms based on AI algorithms, which are able to generate novel enzymes, synthetic biology evolves from being a modification of existing forms of life into a tool for addressing humanity’s complex problems.  By programming bacteria with specific instructions, we can make them work in ways other drugs normally can’t. While there are still challenges in the field, continued research could make engineered bacteria a viable option for patients soon.

ACKNOWLEDGEMENTS

Thank you to When Cells Resist for an awesome article idea, memorable illustration and a wonderful collaboration experience.

Support the When Cells Resist Team:

Instagram @whencellsresist

When Cells Resist Web Blog

SOURCES:
https://www.creative-biolabs.com/blog/index.php/three-major-challenges-in-synthetic-biology/

https://www.neb.com/en-us/tools-and-resources/feature-articles/programming-life-inquiry-and-engineering-through-synthetic-biology?srsltid=AfmBOoqArd5illUhQjEbyYmScrZ8FMCIKS7kl_l9Xq4BJ8oLlCVnyY3s

https://www.ted.com/talks/tal_danino_programming_bacteria_to_detect_cancer_and_maybe_treat_it

Cambridge A Level Biology Textbook

https://www.youtube.com/watch?v=2DgVdxAZFsI

https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/dna-and-rna-structure/a/prokaryote-structure

https://www.lesswrong.com/posts/wpRP44NT6kHaKNdnn/why-are-bacteria-so-simple

https://quadram.ac.uk/understanding-how-bacteria-come-back-from-the-dead/#:~:text=Bacteria%20can%20multiply%20rapidly%2C%20potentially,20%20minutes%20in%20ideal%20conditions.

https://www.google.com/search?q=how+often+do+eukaryotic+cells+divide&rlz=1C1OPNX_enUS1082US1082&oq=how+often+do+eukaryoti&gs_lcrp=EgZjaHJvbWUqCAgCEAAYFhgeMgYIABBFGDkyCAgBEAAYFhgeMggIAhAAGBYYHjIICAMQABgWGB4yCAgEEAAYFhgeMggIBRAAGBYYHjIICAYQABgWGB4yDQgHEAAYhgMYgAQYigUyDQgIEAAYhgMYgAQYigUyBwgJEAAY7wXSAQg0MTAyajBqN6gCALACAA&sourceid=chrome&source=chrome.ob&ie=UTF-8

https://uwaterloo.ca/news/media/beating-cancer-eating-cancer

https://asm.org/articles/2020/june/how-quorum-sensing-works

https://synapse.patsnap.com/article/what-is-a-dna-synthesizer-and-how-is-it-used-in-synthetic-biology

Firing thousands of acoustic beams simultaneously, an Echoscope generates high-definition, real-time 3-dimensional images of underwater landscapes, even in murky, low-visibility waters where human eyes and traditional cameras fail to capture their surroundings.

One of its most fascinating capabilities is mapping out hidden subsea sceneries and undiscovered historical shipwrecks. Apart from finding static artefacts on the sea floors, marine researchers and operators using Echoscopes can actually render moving objects in 4D. This allows scientists to monitor elusive marine life hidden amongst deep sea structures, inspect delicate coral reefs without causing any damage to them and detect subtle gas-leaks or micro-features in intricate underwater terrain, capturing it all in the form of a continuous under-the-sea 3D movie.

Echoscope is also the name of an alternative segment of the weekly Saturday articles. In this series, SPLICED will feature interviews with researchers, professionals and scientists from a plethora of diverse biological backgrounds with unique and truly insightful stories to tell. The signature type of publications will all the same continue.

The Chemistry of a Biological Cell

All biological functions are powered by chemical reactions- also known as metabolic reactions when they occur in living bodies. The chemistry of a biological cell relies on four main types of biomolecules: carbohydrates, lipids, proteins and nucleic acids.

Life blossoms from biology and biology is powered by the principles of chemistry. At the core of every biological process that allows the functioning of all living systems are biochemical reactions.

Various cellular and biological processes’ main mechanisms rely on chemical changes, making chemistry a crucial requirement for understanding how biology actually works.

Ranging from molecular phenomena occurring the same as they did millions (or even billions) of years ago, to the simple mechanics that allow us to move, communicate, eat and even process emotion, chemistry remains the silent director of all living structures, orchestrating it all behind the scenes.

Dr. Annika Evans

Bridging the interface between science, technology, communication and artificial intelligence, Dr. Annika Evans is a PhD level bioengineer and industry scientist who also writes for biotechnology professionals.

She is also the author of The Biotech Tea on Substack.

below is the interview in a (question + answer from the scientist) format:

1. If you had to explain your current research using only objects in a kitchen, how would you do it?

Analytical development is all about developing robust lab protocols that are used to characterize a drug.

Not only the ingredients that go into the dough but the way they need to be prepped (Sift the flour? Soften the butter? Brown it?), the order you mix them together, and the temperature of the oven. A cookie is only as good as a recipe. Data is only as good as the lab protocol.

2. What is one problem your work could potentially solve in 10 years?

A lot of my work is now working to incorporate AI agents into removing inefficiencies in documenting the work we do. The most impactful work comes from directly being in the lab running experiments and strategizing ways to be innovative. The time spent writing the protocols and reports is one thing that should take less time and I hope to solve some of that.

3. Is there a moment in your research where you completely failed, and what did that failure actually teach you?

Many times! Failing makes you comfortable with failing! And negative data is honestly just as useful as positive data. Sometimes scientists find answers by process of elimination.

4. If you were 16 again, what is one biology-related skill you would start learning today?

Gene editing is such an important field within biotech. Understanding the fundamentals of cell biology will help you have a solid base for getting into the more complex aspects of gene therapy. I also think chemistry is extremely underrated and helps take your understanding of cell biology a level deeper.

When it comes to skills, teach yourself a little about PCR! It’s a fundamental skill that you’ll absolutely use someday.

Takeaways

The laboratory protocol is just as important as the main investigation or findings themselves. These documents help evaluate the results by displaying the exact measures taken to obtain them, building credibility by showing consistency in the methods or approach.

By disproving a hypothesis or realizing a fault in a methodology, a scientist contributes by establishing some things that should not be done or be done differently, saving time and energy in the future.

AI optimization in various industries will be incorporated — not to reduce the amount of work that is to be done but to eliminate a major segment of repetitive, no-brainer tasks to allow focus for a longer duration on the main agenda.

Acknowledgements

Thank you to Dr. Annika Evans for her informative and honest answers.

Check out The Biotech Tea

Sources

What is the mechanism of Echoscope?

Hydrographic Surveying and Mapping

Meet The Future Of Visualization And Mapping Sonars

Underwater SLAM and Calibration with a 3D Profiling Sonar - ADS

A magnetic field is an area inside of which anything with magnetic properties, any magnetic material or an electric charge experiences a change. In other words: electricity, a magnetic conductor or another magnet experiences change in a region classified as a magnetic field.

On Earth, the arrangement of the magnetic field is as if a mostly uniform mesh was wrapped from east to west and the top and bottom were concentrated at the north and south poles to ensure they all connect and no mesh remains outside the spherical shape. The lines of the mesh here represent each magnetic field line; compasses and similar utilities use these lines to operate.

Animals such as sea turtles, flamingoes, birds and even bacteria migrate using Earth’s magnetic field. Populations migrate together from one initial location to another suitable one due to lack of resources or change in season. This isn’t possible because all of these animals evolved with a compass or a version of Google Maps wired into their brains; the real reason is much more fascinating and unbelievable: they display something known as magnetoreception.

In this phenomenon, there isn’t one singular biological compass in one individual from the community or population, instead, each member the troop possesses multiple tiny compasses that work at a cellular level allowing them to align their survival instincts to the guidelines provided by the planet.

For years, it was know n that species migrate with the help of Earth’s magnetic field but it was long after that scientists determined how exactly this occurs. We also assumed that us humans were blind to Earth’s magnetic fields without technological or human-made tools. What we thought was a biochemistry problem emerged to be a cutting-edge mystery involving quantum biology. Birds played a major role in pioneering the path to this significant discovery through an observation involving their eyeballs.

Cryptochromes: the starts of the magnetoreception show.

These are specialized proteins found in the eyes of birds that are activated when exposed to blue light. When activated, these proteins trigger the formation of entangles electron pairs that make the body of the organism sensitive to magnetic field lines.

Upon investigation, it prevailed that humans too have this special blue-light-activated protein although, it hasn’t been activated and continues to remain dormant currently. Upgrading to a deeper understanding on how animals navigate through these cryptochromes and electrical signals unlocks an entirely new field where biological systems intersect the establishments of physics: Quantum Biology.

This new field opens opportunities for researching about how living things can embrace bizarre and unexpected mechanics like electron entanglement all at room temperature. Furthermore, understanding magnetoreception is crucial as our world fills up with electromagnetic noise (5G, Wi-fi, power grids). Getting a grip on how these invisible navigators function allows the protection of migration ecosystems and figure out what artificial magnetic fields are actually doing to the bodies of humans and the beings surrounding us.

Now we know birds (and possibly many other animals) don’t just look at the sky and follow their gut instinct. Instead they read a map written in quantum mechanics and powered by blue-light receptors.

The same superpower remains waiting to be activated in humans right now.

Sources

Understanding magnetoreception - YouTube

Through the previous few times I’ve written about the versatility of bacteria and some impressive things they can do, it is undeniable that these tiny invisible creatures possess an abundance of underrated skills and power.

For example, bacterial populations carry out a process called quorum sensing which is similar to taking a popular vote to determine what action they perform next as a whole.

They are also proven to be a synthetic biologists best friend. Synthetic biology utilizes natural substances, microorganisms and processes from nature to develop technologies for modern problems. Bacterial cell DNA can be easily experimented with while staying within ethical bounds, making these unicellular organisms foundational for research and manufacturing.

More specifically, thermophiles are the category of bacteria that inhabit locations with extreme conditions. Mini citizens of volcanic craters and hydrothermal vents have aided scientific development in many ways: from biosensors to metabolic engineering and even applications in medical device manufacturing.

Thermophiles (heat-loving bacteria) are like the desert dwellers of microorganisms.

Bacteria that can withstand high amounts of heat, often called extremophiles, are used to manufacture heat-resistant enzymes for industrial purposes. Most enzymes (catalysts that speed up reactions) denature and disfigure when conditioned to a temperature greater than their optimum.

Extremophiles on the other hand can operate at temperatures hot enough for lava to be in liquid form in, hence, making them suitable for catalysts in industries. These creatures, used as extremoenzymes, are usually dwellers of volcanoes and hydrothermal vents.

Fermentation in factories - a process done to produce organic substances/ solutions ethically using bacterial cells’ genome - can be done using thermophilic bacteria for a higher success rate and yield since temperature fluctuations do not hinder bacterial growth.

Tectonic Activity

Volcanoes are essentially openings in the Earth’s crust leading to the core. When tectonic plates below the planet’s crust collide or move, at times it results in a volcanic eruption.

These fiery formations also release biproducts upon reigning lava on everything within a few kilometers from them. Including gases, ash and energy-rich environments, volcanic activity provides scientists that study the Earth loads to work with. Volcanic cities and towns also develop patterns and habits in daily lives of citizens which is one of the reasons as to which they are helpful to historians and excavators.

Some common gases, some familiar names: carbon dioxide and sulfur dioxide. Synthetic biologists have succeeded in utilizing these previously unimportant gases to program engineered bacteria to convert industrial greenhouse gas emissions into usable bioplastics and biofuels.

Want to know how life on Earth originated?

Volcanic activity- the chain reaction involving tectonic plates, high pressures and thermal outlets on the Earth’s surface- created a high-energy, harsh environment similar to ones surrounding volcanoes on prebiotic Earth.

Prebiotic refers to ‘before life’: the time during which our oceanic planet was a mere rock undergoing cooling on its surface.

Volcanoes existed. Bacterial populations- not yet.

The energetic conditions generated by volcanic eruptions have been used in many experiments with the aim to simulate the qualities of prebiotic Earth.

One popular experiment is the Miller-Urey model of prebiotic Earth that aimed to synthesize organic molecules (such as amino acids that make up proteins) through subjecting the mimicked prebiotic conditions to lightning. Miller and Urey’s studies have allowed us to learn many things about Earth before water, life and humans took over.

Yet, the confirmed origin of life is not known although it is hypothesized to have begun from cyanobacteria in high pressure regions of hydrothermal oceanic vents.

Miniature Mining Machines

Nanoparticles produced due to this natural event is used in syn-bio as a template to enable bacteria to synthesize size-controlled nanoparticles of metals and more for medical and electronical devices.

An erupted volcano results in rare Earth metals around the area of impact. Scientists have used principles of synthetic biology to give rise to bacteria that can leech into ores and extract bits of metals, making them mini mining machines. They do this by secreting organic acids and producing metal binding proteins as instructed by their genetic material which has been modified by experts.

This makes it so that humans do not need to enter mild conditions to locate these semi-precious metals. Bacteria do all the heavy lifting.

cGAS-STING

Volcanoes remind me of a biological phenomenon that occurs right inside our body cells.

An immune response that goes all out when unknown/ foreign DNA is detected.

DNA, when mutated (randomly changes at least one base pair or one letter in the code) leads to cells with the wrong DNA dividing and multiplying which eventually causes cancer.

Hence, to prevent disaster, the human body has defenses in place. The cGAS-STING pathway which is triggered instantaneously when an imposter genetic code is found during the cellular multiplication process.

DNA is only supposed to be in the nucleus or the mitochondria of animal cells. When it leaks outside the nucleus into a space known as the cytoplasm, the cGAS protein binds to it acting as an indicator/ marker.

To help, cGAS creates a tiny molecule as a messenger called cGAMP.

This then activates STING which sends signals to produce inflammatory proteins and interferons that stop the cell from dividing by causing it to explode.

Yes- cells can cause themselves to detonate completely to save the entire body from the risk of fatal disease.

Discovering this pathway has been extremely important.

Drugs are being developed in order to trigger this mechanism in potential tumors in the body that lets cancer kill itself by fully destroying the foreign cells, fixing the implication reinforcing a natural bodily defense.

A second chance using cGAS-STING with a much higher probability of success.

Sources

Next-generation biotechnology inspired by extremes: The potential of extremophile organisms for synthetic biology and for more efficient and sustainable biotechnology - PMC

Extremophiles: Unlocking biomedical and industrial innovations from life at the edge

Synthetic Biology of Thermophiles: Taking Bioengineering to the Extremes?

Volcanic gases can be harmful to health, vegetation and infrastructure

The Miller Volcanic Spark Discharge Experiment

Everyone adores it - the fruit that feels like sunshine encapsulated.

The combination of the universal favourite shade of bright yellow alongside its unforgettably sweet, refreshing experience and the memories associated with it, mangoes are called the ‘King of Fruits’ for a reason.

Your midsummer evening snack in the trenches of June and July.

The contents of DIY popsicle moulds and on the skewers of ‘fruit-rockets’.

Elevating cakes, pastries, pies, sweets and milkshakes.

The popular fruit is very well known for its abundance of vitamins A and C; these support immune function and combat age-related vision degradation.

Fruit stationery

A mango tree as a whole does not only contribute wood and nourishing fruits; organic waste of mango trees are transformed by local and national craftsman owned brands into usable stationery and school supplies.

From parts of the mango tree which would otherwise be disregarded or managed poorly, useful and eco-friendly paper and wood products are made instead.

The process involving extracting cellulose fibres from agricultural waste, such as pruned twigs, bark, fallen leaves or seed kernels, prevents waste burning and reduces reliance on only wood pulp to manufacture paper-based products.

1. Harvesting of Raw materials: Materials considered waste are collected from processing units or orchards, segregated and chipped to small, coin-sized chips.

2. Fiber Cooking (pulping): One type of the sorted prior waste is boiled in alkaline solution, breaking down lignin (natural glue). Next, they are washed using water to remove chemicals and residual lignin to achieve clean cellulose (made of intertwined chains of glucose molecules- material of plant cell walls) pulp.

3. Refining and Filtration: The pulp undergoes a mechanical blender that thins the substance. Additional components such as waste office paper or recycled rags are added to improve flexibility.

4. Sheet Formation: Refined mango pulp is dissolved in a large amount of water in a wide Vat. A paper maker with a mesh screen lifts paper pulp from the solution, ensuring water can leave through the mesh openings.

5. Pressing and Couching: A hydraulic press is used to apply pressure onto the pulp sheet covered with felt sheets to remove excess water and compress it into a compact sheet. A uniform layer of interlocking mango fibers forms.

6. Drying and Completion: The sheets are removed from in between felt, dried flat and coated to prevent ink bleeding through. Smooth rollers give it a sleek, uniform shape.

A Future Full of Mangoes

For many, mangoes mean summer, cooking and desserts, however, the fruit offers much more than sweet flavour. Each part of the mango tree can be used for its potent pharmacological properties, such as being an anti-oxidant and anti-inflammatory.

Anti-oxidants inhibit compounds known as oxidative agents that undergo a reduction-oxidation (redox) reaction with bodily cells, causing harm to tissue and potential damage. Many naturally found sources of nutrition contain anti-oxidants that react with the oxidative agents instead of body cells to deactivate them, preventing excess oxidation reactions.

Mango rind is rich in exceptional bioactive plant compounds called xanthones; more specifically: y-mangostin and a-mangostin. These offer significant health and medicinal benefits.

Isolated and extracted xanthones have been found to suppress markers of inflammation in the body. This property is used in traditional medicine to soothe skin inflammation or wounds.

Some studies suggest that y-mangostin and a-mangostin prevent rapid proliferation of cells (a very fast increase in cell multiplication rate), potentially being anti-cancer since these xanthones are also pro-apoptotic (cell death promoters).

Compounds from the pericarp, leaves and wood have displayed, in various studies, anti-microbial and anti-viral properties alongside proving themselves neurocognitive function supporters.

Designer scents

Mango pulp has played a significant role in the metabolic engineering of flavors and fragrances.

Synthetic biologists can now insert genes from mangoes into bacterial cultures to enable a sustainable, cell-free fermentation of universally amiable scents and flavors without harvesting the fruit.

Plastic for good

Rich in reducing sugars and pectins, mango peel waste is transformed into bioplastic which is 100% biodegradable. PHAs (polyhydroxyalkanoates) found in this type of bioplastic allows it to be durable, lightweight and fully decomposable.

Syn-bio-sensors

Fruit derived nano-particles mixed with metal salts are incorporated into biosensors to efficiently detect the presence of pathogens (disease causing microorganisms). All without the need for toxic chemicals.

References

Medicinal properties of mangosteen (Garcinia mangostana)

Synthetic-bio for Agro waste Startups

Chemical composition of Mango

Mango byproducts for sustainable bioactive packaging

Robotics meets Cellular Biology

Innovations are usually credited to the individual that is able to explain them, sell an idea or patents the plans. However, most innovations have not one, but many stories that inspired their creation and lead to a vision transcending into reality.

Similarly, in the case of organs-on-chips, a student’s elaborate school project inspired their professor to explore a new kind of possibility that the world of science hadn’t experimented with before. More specifically, in 2007, Harvard professor Dr. Donald Ingbur and postdoctoral fellow Dr. Dan Huh were encouraged to combine micro-scale engineering with living cells as done by a student who sought to simulate lung passageways by incorporating living cells on a non-living microfluidic prototype.

In 2010, Ingber and Huh successfully created the first ever Lung-on-a-Chip. Using suitable materials and bioengineering and synthetic biology principles, they had figured out a way through which humanoid organs could be accurately simulated completely separated from the human body. Though the organoid is not 100% independent or self-sufficient (powered by a computed chip), its tactile properties are indistinguishable from the ones of a real human lung.

The prototype looked like this:

The scientists had made a small, flexible, silicon chip approximately the size of a USB memory stick. This was translucent and contained hollow micro-channels separated by porous membrane much alike to the structure of lungs developed in a healthy adult human being.

Not long after, living lung cells were cultured on one side of the engineered chip while blood vessel cells were cultured on the opposite side. By utilising vacuum chamber technology, the team was able to mimic human breathing, causing the lungs to expand and shrink periodically synchronised with the blood vessels.

The compatibility of the synthetic lungs were tested and compared with results obtained by lungs inside a person in various surrounding air conditions. Additionally, bacteria and immune cells were also introduced into the system to add to the accuracy of tissue composition (the types of cells and their amounts that make up the lungs). White blood cells were observed and were seen moving through capillary walls, engulfing pathogens and functioning normally, making the organ-on-a-chip project revolutionary.

Nowadays, this technology is still relatively rare, however, scientists and immunologists collaborating with biological engineers have successfully simulated multiple other fundamental organs in vitro (biological organs/ processes occurring or made to occur outside a living system). We have developed synthetic livers, stomachs and hearts; the field of biomedical engineering has therefore grown exponentially popular in the past decade.

Dogs, Rabbits and Ethics

Why is the invention of computer powered organs important?

As it allows us to simulate human bodily conditions using no real living species, testing of drugs and products on animals becomes less desirable.

For decades, testing cosmetics, treatments and newly developed therapies have been done using the creatures that provide the closest replica of how the real human target organ would respond. Dogs, rabbits, monkeys, rats, guinea pigs. Though, testing on any animal is ultimately risky and poses the obvious ethical concerns; multiple species that are now endangered currently face the risk of extinction due to too many of their kind in captivity or in laboratories.

Although all products had to undergo evaluation before contacting a human system, animal testing has proven to be an inaccurate representation of the human body’s response to a certain product 92% of the time. Only 8% of animal tested products prevailed. Hence, a better, more ethical manner of testing was overdue.

While protecting these species from disease and endangerment, since computed organoids are engineered to simulate human organs, the accuracy of results obtained are greater. More reliable, ethical and efficient.

AI-Generation in Medicine

Though the title may be counterintuitive, artificial intelligence usage is growing rapidly in a plethora of fields including drug testing and evaluation; AI is used to model outcomes based on existing knowledge of drug-organ interactions.

The irony is that the data processed by AI is obtained through perviously done medicinal and product testing on animals (which has a very high inaccuracy rate). However, AI models are being curated and are advancing implying they may predict outcomes solely based on chemical and biological properties and facts instead of preexisting incorrect databases.

AI is unavoidably still capable of making mistakes or miscalculations but is nevertheless more reliable than animal testing. Animals have slightly different organ systems and arrangements while computer simulations can be manipulated and adjusted as per requirements.

Due to the flexibility and scope of computed organoids, this innovation opens doors for personal medicine; one small step by a Harvard student and a giant leap for the expanding developments in personal medicine. Organs-on-chips can be made to any size and other specifications curated to the patient making targeted therapy testing for rare diseases a more streamlined process while reducing stress on the patient and caretakers.

Unsolved Mysteries

The human body however, does not consist of only one isolated organ. Instead, it comprises if multiple organ systems interacting and co-depending on each other; a malfunction in another organ can affect the target organ directly; this is where organs-on-chips fail to predict with full accuracy.

We are yet to develop or ameliorate an AI model or engineered organ that simulates the entire human body ecosystem. This is difficult for many reasons including the microscopic nature of cells and other structures, blood vessel networks reaching all corners of the body and simulating a brain and a nervous system.

Complex and intricate, containing millions of cells prone with metabolism sometimes to error, the behaviour of the body as a whole is ultimately unpredictable by the singular synthetic organoid. This paradox remains unsolved till date.

Sources

1. Microfluidic devices for Biomedical Applications

2. Organs on a Chip- The Future of Drug Development

3. Organs-on-a-chip: the collaboration between engineering and biological systems

4. Organ-on-a-chip revolution

How often on the news do you come across a disheartening headline featuring the destruction of nature?

From accidental oil spills to deforestation for urbanization, these large-scale preventable catastrophes leave lasting scars on our environment.

While news articles only cover 5% of major oil spills globally, the 95% consisting of illegal land dumping, industrial waste disposal and operational leaks impact habitats just as much although they are rarely under the limelight.

99% of Earth’s population breathes air that exceeds established health quality limits.

80% of all European soil used for agriculture has been found to contain pesticide residue.

10,000 tonnes of oil spills into our oceans annually.

About 16% of agricultural soils exceed global safety thresholds in concentrations of metals and contaminants.

The statistics are well known and advocated; but are measures being taken to control unforeseen circumstances?

Nature’s cleanup crew

Bioremediation is a broad term describing the methods used to remove environmental pollutants, detoxifying soil, air and water using organic, eco-friendly compounds from microbes — mainly fungi and bacteria and sometimes specific plants as well.

These organisms are proven to convert toxic, poisonous substances into harmless byproducts such as water, carbon dioxide and microbial biomass.

At certain optimum conditions, these microbes are able to digest hazardous chemicals and repurpose them as an energy source, breaking them down biochemically, preventing negative impact on the surrounding flora and fauna. All conditions such as temperature, soil pH, water availability and several nutrients found in soil must be within specific ranges for the conversion process to be initiated.

Bioremediation is classified into two main divisions based on where the treatment process is conducted:

• In-situ: Treatment of the contaminated site occurs directly at its location, minimizing disruption and transport/ laboratory costs. An example of this includes bioventing, in which air containing nutrients is supplied to existing soil microbes to promote the cleansing of their surroundings. By changing the chemical composure of the toxins directly, the method provides a lasting solution in comparison to recycling or relocation.

• Ex-situ: Affected soil or groundwater is excavated or pumped to enable treatment elsewhere, often in a laboratory where conditions can be better controlled, maintained and monitored closely. Extraction, transportation and treatment costs of this alternative are significantly greater, however it offers more accuracy and a higher, more promising success rate. Complex combinations of contaminants concentrated in the same area require customized treatments, which is where this way of performing the breakdown and purification offers advantages.

Biology of repair

Bioremediation can be further categorized by the techniques by which it is carried out/ initiated. There are various methods that highlight microbes as the protagonist with super powers that only activate when certain environmental specificities are met.

1. Bioaugmentation

   When specific pollutants are detected in soil/ water bodies and become a threat to its ecosystem or a toxicity concern, microbes engineered and modified in the laboratory are introduced to the site to start the decomposition of the pollutants. Since scientists can now engineer microorganisms to conduct various functions through synthetic biology breakthroughs, they can also be modified to adapt to the exact conditions at the site of pollution. Bacteria or fungal cells’ DNA are made to produce certain proteins that aid in the breakdown of the exact unwanted compounds.

2. Biostimulation

   Microbes are already present in soil and water bodies prone to pollution but usually have insufficient resources or conditions that initiate toxic chemicals’ breakdown. In this method, nutrients such as nitrogen and phosphorus are injected into the polluted sites (sometimes electron acceptors such as oxygen) to stimulate dormant microorganisms to start bioremediation. This is more cost-effective, relies less on precision but depends on well-calculated amounts and concentrations of the provided nutrients.

3. Phytoremediation

   Unexpectedly, green plants and trees (that contain chlorophyll) are planted strategically, enabling them to absorb and breakdown contaminants by photolysis (breakdown using absorbed energy from light — in this case from the sun). Instead of being affected by the toxic discarded chemicals, plants use their photolytic ability to restore the organic composition of their soil.

Microbes at the end of the world

With minor assistance from humans, nature can filter out and process contaminants, replenishing the land’s ability to house its plants and animals. Though there are multiple methods to ensure waste is managed in an eco-friendly way, human activity leading to toxic chemicals being released should be tackled at its origin.

Via bioremediation, humans can collaborate with nature instead of sabotaging it using processes that are already programmed into microorganisms; synthetic biology offers experimentation and further control in the same.

Though this ingenious solution relies heavily on precision in quantities, concentrations and environmental climate and circumstances, future developments in biological technologies may prevent harmful substances from ever being discarded into essential ground and water bodies. Promising development on more efficient and successful bioremediation processes is underway facilitated by syn-bio, microbiology and bio-engineering.

Summary

• Pollution’s various forms contribute to some of the most escalated global environmental problems.

• Bioremediation utilizes modified/ dormant microbes or plants to decompose harmful chemicals in soil and water bodies.

• This cheaper, eco-friendly method depends heavily on if the conditions are within optimum range.

• Few of the multiple techniques of bioremediation include bioaugmentation (introducing engineered microbes to sites), biostimulation (providing external nutrients to dormant microbes in polluted sites) and phytoremediation (specific plants that absorb and breakdown chemicals are introduced).

Dig Deeper

Bioremediation

Bioremediation, Meaning, Process, Types, Techniques ...

What is Bioremediation?

Bioremediation, a broad perspective - PMC

Bioremediation: The pollution solution?

Contrary from popular belief, matcha was first prepared in China during the premodern period when the country was under rule of the Tang dynasty. Monks, royals and figures of high stature used to steam green tea leaves that were dehydrated and powdered.

Originally, the beverage was prepared using the powdered matcha and hot water in a ‘Kumi-dashi’ (shallow, handle-less cups used in Japanese, Chinese and some east-Asian cultures to serve drinks to guests and important people). Bricks of the green tea powder were introduced during this era from approximately the 7th to the 10th century (600 AD - 999AD).

The development of matcha as we know today has been shaped by not one - but many - dynasties over time. After the Tang dynasty, the royals of the Song dynasty began preparing the green tea powder with a whisk and hot water, utilizing the beverage for medicinal and therapeutic practices.

By the time the tea grew popular and was thriving in Japanese culture in the 16th century Muromachi period, it faded significantly as a part of chinese routines. Farmers in Japan discovered a way to preserve and increase the vivid green colour of the tea leaves by keeping them under shade from the sun. The leaves grown in controlled sunlight produced the bright, modern matcha-green pigment used commercially in today’s world.

Though the ancestral origin of matcha lies in ancient China, the celebratory tradition of the Japanese tea ceremony caused the drink to become well-known among the country. Though cultivation and preparation techniques are ever-changing — from sun drying and grinding to processing in industrial grade machines — the fundamentals of what makes a cup of matcha classify as itself remain with the Japanese way of preparing it.

Pinterest-worthy

The calm, pastel green of matcha when served with milk and other add-ons as well as its reputation as a healthier and more effective version of coffee has popularized the beverage as part of daily routine for gen-z. Its colour and presentation with various flavours that have emerged following the rising trend of matcha make it highly photogenic and sharable on social media.

Priced similar to coffee cups, matcha additionally provides the sense of an affordable luxury, feeling like a ‘little treat’ or as focus-fuel unlike coffee which causes a quick-release spike in caffeine leading to jitters.

Gen-Z reinvented matcha as a part of the wellness or ‘clean-girl’ aesthetic. Moreover, it is also seen as a superfood rich in antioxidants that support a wellness-oriented lifestyle. Content creators and health influencers play a significant role in the surge of daily matcha consumption as a lifestyle trend.

Much alike to the romanticization of digital cameras, matcha arose from its Japanese cultural roots to becoming a global culinary sensation. As trends recycle themselves every few decades, they also return redefined and modernized; in this case from a Kumi-dashi to a coffee cup.

Versatile green drink

The versatility of the drink that revolutionised routine caffeine consumption can be defined in two ways; its trendy, innovative flavours and stylistic compositions or its surprisingly powerful medicinal properties.

Most metropolitan cities now have franchises exclusively focused on matcha as their primary product. Increasing demand for items like matcha powder, sifters and organic unprocessed matcha powder create new business opportunities.

Depending on the location, matcha comes in a plethora of varieties; classic, latte, cold foam, white chocolate, vanilla, mango, berry, birthday cake, cheesecake and many more — the options are endless.

While its picture-worthy looks contribute to the appeal, scientists in laboratories have different aims and ways of using matcha for scientific advancement.

Many manufacturers have begun combining the natural green tea powder with extra collagen and antioxidants, making it aesthetic and healthy (in moderation) adding to the product’s value and benefits.

Synbiotics is a term used to collectively describe prebiotics and probiotics - food groups that are highly beneficial to the gut microbiome. Mainly consisting of compounds derived from mushrooms, ‘MycoSynergy’ is used in matcha powders for added advantages. By mixing matcha and synbiotics, brands can obtain a wellness evoking superfood powder that can be used in beverages, as a coffee alternative, in milkshakes and even some desserts or dishes.

Not only is the beverage great for gut health when taken in controlled quantities, specific enzymes naturally found in matcha have proven to be fruitful in skincare and dermatology products - whether cosmetic or medicinal. These enzymes offer functions such as sebum control, gentle exfoliation, pore unclogging and are wonderful natural scrubs that clear dead skin cells without rupturing the tissue underneath.

Matcha vs Cancer

Studies conducted on the effect of matcha on metabolic activity strengthen its title as a superfood for healing and wellbeing.

1. Matcha acts as an anti-inflammatory agent resulting in lesser chances of obesity-related health implications mainly due to its collaborative function ameliorating the gut microbiome.

2. Research indicates matcha caused positive effects on the brains of mice, suggesting cognitive and neural benefits.

3. Matcha has been proven to help alleviate NAFLD (Non-alchoholic fatty liver disease) caused by the accumulation of excess lipids in the liver. Similarly, it can reduce chances of CHD (Coronary heart disease) which is also a result of a diet consisting of excess fats and oils.

4. Cancer researchers investigating the effect of matcha compounds on a tumor (growth of mutated cells) found that matcha extract can effectively propagate and inhibit the formation of breast cancer at the root (starting stem cell). The bioactive compounds and pigments that matcha contains enable it to do so. Its powder when dissolved has three times more catechins than normal green tea as well as polyphenols that reduce free radicals (compounds that damage DNA due to their high reactivity).

Dig deeper

1. Cancer Research UK

2. Therapeutic effects of green tea

3. Testing anticancer effects of matcha on zebrafish

4. Chemotharpeutic properties of matcha

A time where the ecoscope proved itself advantageous was when the system was used by European and American teams of researchers to record and monitor how pollution levels impact the behavioral patterns and migration of juvenile glass eels. The remote operated device facilitates observation of marine and aquatic habitats without causing significant harm or polluting the oceans.

By developing understanding on migration patterns, human activity’s influence on ecosystems and biodiversity changes’ relation to urban activity, we can better design our systems and technologies to reduce overall environmental impact and sustain a plethora of species in global ecosystems, orchestrating naturally.

Ecoscope is also the title for the series on SPLICED. in which interviews with experts working in biology are featured alongside advice from the experienced biologists, making their research more accessible to a wider range of science-keen readers.

Echoscope is an alternative segment of the weekly Saturday articles. In this series, SPLICED will feature interviews with researchers, professionals and scientists from a plethora of diverse biological backgrounds with unique and truly insightful stories to tell. The signature type of publications will all the same continue.

Cancer and The Cell Cycle

Our body is made up of cells- some specialized and some unspecialized. Most cells divide to multiply and keep the cell life cycle continuous. However, certain types of cells such as nerve cells or neurons don’t divide into new neurons- instead, they die and are replaced when their singular cycle terminates.

Cells that do divide to reproduce undergo division by either mitosis (multiplication division) or meiosis (reduction division).

During mitosis, cells duplicate (double) their DNA and organelles, making exact replicas to ensure that two identical daughter cells are formed when the parent cell separates into two. The new cells are genetically identical to the parent cell and each other. The equation depicts how the division of a single cell occurs where 2n corresponds to the amount of chromosomes in a diploid (normal) cell.

During meiosis, DNA is doubled however, four daughter cells are produced finally instead of two. When four cells are produced from the doubled DNA of one cell, the resulting daughter cells have half the number of chromosomes (stores of genetic information/ DNA). The equation depicts how meiosis occurs with an additional division where n corresponds to the number of chromosomes in a haploid (germ) cell.

Meiosis does not result in identical daughter cells since the genetic material in the cell become scrambled due to exchanging of DNA segments before division; this makes all four resulting cells genetically different from the parent cell and each other.

Both cellular division types consist of many stages and intricate processes at cellular level; all processes must be coordinated and precisely function to ensure that a cell receives the correct amounts of DNA, organelles etc. Regulatory mechanisms hence exist to prevent the formation of defaulter cells. Chemicals at every stage of the cell cycle ensure everything is on track; if any faulty/ unordered factor is detected, the cell’s cycle is terminated and the cell dies.

In some instances, these regulatory mechanisms let faulty cells bypass causing an imposter cell different from the cells in the tissue around it.

When abnormal cells are able to sustain themselves, they multiply through meiosis rapidly to produce more copies of itself. Cancer refers to a large group of diseases cause by the rapid, uncontrolled division of abnormal cells in the body leading to their growth and spreading.

These unauthorized cells ignore regulatory signals, refuse to die and terminate their cycle and continue dividing at a faster rate than normal cells. Eventually, the mass of cells may develop into a tumor in some types of cancers.

Think of the mobile game ‘Among Us’ in which a small fraction of players are the imposters that eliminate players that are crewmates to outnumber them before they are detected and voted out. Cancer is when the imposters multiply, reducing available resources for the crewmates and gradually causing significant damage to the spaceship.

Gerome Romero

1st year PhD Candidate in Biological Chemistry under Biosciences at University of Utah

Researching to potentially uncover new therapeutic strategies for cancer patients, the featured scientist aims to impact the lives of many living undergoing cancer treatment with ameliorated methods designed for an individual’s biology. Mr. Romero also shares helpful insight on being a PhD student along with thoughtful advice on skills one should start learning earlier in their academic journey.

Below is the interview in a [question + answer by the scientist] format:

1. If you had to explain your current research using only objects in a kitchen, how would you do it?

They crank the stove up too high, keep cooking nonstop, and make way too much of certain dishes—sometimes burning things, sometimes flooding the kitchen with stuff no one ordered. They also ignore the head chef (your body’s regulatory signals) who’s trying to keep order.

My research is like figuring out:

Which cooks went rogue (identifying the mutations or pathways involved)

What recipe they’re misreading (understanding the faulty instructions in DNA or signaling)

How to stop them without shutting down the whole kitchen

2. What is one problem your work could potentially solve in 10 years?

This may sound very optimistic but my current research will potentially solve the pack of therapeutical strategies to combat different types of cancers.

3. Is there a moment in your research where you completely failed, and what did that failure actually teach you?

I think one of the most common things that happen as a PhD student is failing whether it be experimental mishaps, classes or even tests. I am very fortunate enough to not have any big failures so far.

4. If you were 16 again, what is one biology-related skill you would start learning today?

Probably reading more publications. There are tons of readings in grad school so it would have been better for me to start that habit when I was younger!

Takeaways

In experimental fields such as bioscience and related research where unpredictability always has a place in procedures and hypotheses, laboratory mishaps or scoring low on assessments are less of an immediate failure but a redirection similar to biological feedback loops. Perseverance combined with consistent efforts is the ‘slow and steady’ in science that ‘wins the race’.

Reading and understanding academic research papers and literature is an underrated and helpful skill to learn when pursuing research-driven areas of science. Intaking the style and presentation of various types of academic papers and publication undeniably enables an easier understanding and composition of papers in the future.

Acknowledgements

Thank you to Gerome Romero for his time and honesty - and for making a restaurant analogy which was indeed memorable.

Follow Gerome’s PhD journey on Instagram:

@geromeunderthescope

Quorum sensing as we know today is the tendency of bacterial populations to intercommunicate and ‘vote’ via chemical signals to decide a collective action.

This discovery made in the late 1960s was not by an individual scientist, instead it was a partnership and alignment of the works of two experts; John Woodland (Woody) Hastings who spent the ultimate years of his flourishing biology career as a professor at Harvard University and Kenneth Nealson who is currently retired after his post as the Professor of Earth science and Biological sciences at University of Southern California.

As Hastings was observing bacterial populations’ effect on bioluminescence, he noticed the patterns between the chemical signals released, concentration of bacterial cells and the degree of luminosity.

Bioluminescence of the ocean is a natural phenomenon that occurs in select locations- usually sea shores- during which waves appear luminescent at nighttime due to a certain type of bacteria present in these select areas in the sea.

Luminescence in nature is seen in many other species including some jellyfish, glowing beetles, fireflies, anglerfish and certain types of fungi. Organisms produce their own light for communication, navigation and survival. Unlike fish or insects or fungi, bacteria cannot individually produce light, instead the population density and the number of bacterial cells that signal their ‘vote’ to begin bioluminescence (or many other bacterial processes) determines whether the ‘law’ passes or is disregarded/ outnumbered by another signal.

Microscopic e-mail

Us humans used to communicate through visual and auditory language. Now we communicate additionally through e-mail, LinkedIn and satellite signals. Bacteria however, cannot talk to each other. As an alternative, they release chemicals called autoinducers that account for a specific function an individual cell in a population is prepared for or the collective expression of a gene that the singular cell wishes to carry out.

Similarly, when a law is proposed in a parliament or courthouse, the participants undergo a formal voting to deduce whether the act or law is to be passed. Autoinducers released by one bacterium are its individual vote.

For an organism to be considered a living thing, it must display the seven life processes: movement, respiration, nutrition, reproduction, sensitivity, growth and excretion. Sensitivity in bacteria occurs through chemical receptors and secretors while in animals there are different mechanisms that respond to environmental stimuli.

Although the processes vary, their primary purpose and goal remain to adapt and change regarding fluctuating and everchanging environmental conditions to ensure survival. All living things communicate within their species and adjust to the conditions in their surroundings.

In places such as the ocean, conditions change daily; between day and night, afternoon and evening, high tides and shallow waters or the presence of other species that affect the temperature and nutrient content of their surrounding waters. To adapt to the changing conditions, organisms have built-in mechanisms to regulate their internal conditions through positive and negative feedback.

Positive feedback is when the body adapts to external conditions by modifying internal ones to maintain an optimal normal atmosphere for metabolic processes. Negative feedback takes place when the positive feedback goes beyond the necessary limit or if the external conditions have returned closer to normal- negative feedback helps bring normal internal conditions back after successful/unsuccessful positive homeostasis.

Homeostasis is the name given to the repeated positive and negative feedback that occurs to achieve optimal bodily conditions when environmental factors such as temperature, pH or humidity fluctuate. For bacteria to carry out homeostasis, the cells in a population release autoinducers to signify their stance in performing homeostasis. If the concentration of the chemical- also determined through receptors- is sufficient, implying majority vote leans toward performing the process, all cells then undergo homeostasis.

Gene switches

Quorum sensing allows a bacterial population to coordinate and be on the same page when conducting various physiological activities including gene expression.

All multicellular species have the exact same genetic material in every cell in their bodies. However, not all of the genes in the DNA are expressed in every cell. This is how your body is able to sustain numerous different types of cells such as blood cells, nerve cells, brain cells or cells lining the intestinal tract.

These cells that have a specific, niche function and physical attributes that account for the function are known as specialized cells; they form when additional genes from the DNA of a cell are expressed (switched on), allowing them to have features that the standard unspecialized somatic cell does not contain, making them adapted for their function.

Cells become specialized depending on their location in the body, surrounding conditions or when chemical signals are released that tell a normal unspecialized stem cell to divide (reproduce) while switching a gene on to result in a specialized cell. Different specialized cells will have different segments of the genetic material switched on.

Bacteria also have many non-expressed genes in their genetic material. Although they are unicellular, the expression of these genes enables them to carry out processes instead of dividing and transforming into a new type of cell. Genes can only be expressed when the majority of the population agrees with performing an action such as symbiosis, motility, antibiotic production etc.

Are bacteria measured in milligrams or kilograms?

Recent studies indicate that quorum sensing via autoinducers occurs within and between bacterial species- not only are these chemical signals a language exclusive to a population, they can also be a method of communicating with another tribe/ republic of bacteria (different species). Further research leans toward confirming that bacterial autoinducers stimulate certain responses in host organisms.

Wave formation falls under the same principles; if enough water has the same energy and direction, a big wave can arise. Or a fictional flower garden of closed buds that require the scent from open flowers to fill the air as a signal indicating environment safety for all the flowers to bloom.

You may have heard of the terms Gram-negative and Gram-positive bacteria. But what do these terms imply? They refer to the structural distinguishing factors between the two main categories of bacterial cells.

Bacterial cell walls are made of peptidoglycan. In gram-positive bacteria the cell wall consists of thick layers of peptidoglycan without an outer membrane while in gram-negative bacteria the peptidoglycan cell wall in much thinner but with an outer membrane. These categories of bacteria appear different when observed through a microscope; gram-positive ones appear purple or blue since they retain the stain while gram-negative bacteria appear pink or red since they retain commonly used red stains better. They also differ in their resistance to antibiotics due to the presence and absence of the protective outer membrane.

What does this mean for syn-bio?

Bacteria have been fundamental for pinnacles in modern biology due to their versatility and eliminated ethical dilemma.

Since quorum sensing relies on the expression of genes in bacteria, synthetic biology can be used to modify and manipulate quorum sensing. Scientists can provoke bacteria to switch on certain genes depending on our industrial/ experimental needs- the bacterial population then follows and is possible only due to their inter-cellular communication through chemical messengers. Scientific methodologies have been discovered that lets us control gene expression and manipulate quorum sensing to build genetic circuits based on a combination of functions already present in the bacterial genome which are yet to be switched on.

Engineered bacteria pose as promising tools for disease diagnosis, biosensor systems and targeted tissue therapies. Bacteria can verify cell density in a location through quorum sensing, allowing them to make calculated decisions on upcoming tasks and function based on surrounding conditions.

When bacteria sense quorum, they link together forming a biofilm- a common example of quorum sensing allowing teamwork within a bacterial population with many uses in medicine and biological sciences. These biofilms resist antibiotics, expanding opportunities for possible research.

We can now alter bacterial metabolism to perform a plethora of tasks; this changes the way we approach problems and solutions in multiple biological and research powered fields. The lingering question remains: are we up for the change?

References

Quorum sensing in bacteria

Progress in and promise of bacterial quorum sensing research

Quorum sensing: cell-to-cell communication in bacteria

Bacterial quorum-sensing network architectures

Bacterial quorum sensing: circuits and applications

fashion (noun) : the style of dressing or behaving that is the most popular at a particular time.

Dinosaur Leather

We know about leather from animals- unethically sourced- used in automobile interiors, designer-wear and fashion-forward boots.

What about one that is made of dinosaur skin?

Crafted using reconstructed T-rex skin engineered using synthetic biology by specialists using fossilized tissue, mimicking the exact qualities and look of the exterior of a Tyrannosaurus-rex, the world’s first luxury product comprising of dinosaur leather had emerged.

The making of this precious, one-of-a-kind product (a handbag) included a process of determining the DNA composition and genetic makeup of the prehistoric beast through computational analysis of gene sequences and AI modelling to fill in the gaps.

Next, a complete collagen producing instruction manual was deciphered by determining the gene sequences and utilization of AI to help map out possible combinations to achieve the completed genetic code. Cells’ DNA was modified to produce the protein for T-rex collagen (a commonly found compound in the skin of many animals- including us humans) to enable experts to cultivate the required substance and reconstruct a similar replica of real dinosaur skin.

This approach is similar to the manufacturing of artificial (fake/ mock) leather which is also cultivated in laboratories or factories. Using the DNA from the skin of the extinct former Earth inhabitants as a template to form a duplicate to process into leather introduces new perspectives in the syn-bio world and the fashion world.

Presented on 2nd April 2026, the luxury bag is a limited edition collectible piece to be auctioned in the near future; it currently resides in the ‘Art Zoo’. While it is the first of its kind, the company responsible for its production will continue to incorporate the newfound, luxurious, art collectors’ dream material into various products to come.

We were able to replicate proteins of creatures no human has ever encountered- what does this imply regarding the newly introduced possibilities in synthetic biology, biotechnology and genetics?

Fast fashion- lingering effect

The hidden cost of bombarding the internet with a new fashion trend every few days is paid by our environment; microplastics in oceans, waste disposed in water bodies and landfills and ecosystems suffering the consequences which are ultimately reflected back onto us. ‘Fast fashion’ is a term that refers to the practice of constantly buying new clothes and discarding old ones in perfectly wearable conditions to prevent being an ‘outfit repeater’ or being seen in the same combination of garments multiple times.

100 billion garments are created each year.

92 million tonnes of textile waste is generated annually worldwide.

The number of times a piece is worn has declined by around 36% in 15 years.

What about recycling?- Less than 1% of clothes are made from recycled materials.

The introduction of sustainable materials and transparent manufacturing processes pave the way for more non-ambiguous clothing tags and a reduced health impact due to our fashion choices.

Toxic chemicals in clothing and textiles directly affect us when we use clothes- compounds can penetrate through our skin and into the bloodstream compromising metabolic activity and disrupting somatic processes. Indirectly, the textile waste disposed unethically impacts marine life and fish that we later consume circling the significant impact back onto the doers.

Pinnacle pioneers

Synthetic biology in the fashion industry began in the late 2000s and early 2010, uprooted by the former research on the growing pressing topics such as sustainability in design and bioengineering.

The earliest companies that showed their commitment toward sustainable fashion include BioCoture and PILI alongside a handful of other major findings drawn from various research indicating the same possibilities.

Founded by Suzanne Lee, BioCoture gained an exponential amount of exposure after a project from 2008 to 2010 that was able to formulate versatile fabric from bacterial cellulose.

Cellulose is a structure found in all plants and some bacteria only. Not all plant cells contain it however, the cell walls of unspecialized plant cells are made of cellulose. The molecule is chains of glucose molecules bound together and woven into a basket-type pattern providing structural and mechanical support to the plant.

PILI, a more known, larger name in the previous decade became renowned and associated with producing the first ever sustainable dyes and pigment for wearables in 2012 from biological organisms (bacteria).

This was done by using enzymes as the scissors and glue to cut an opening in a strand of bacterial genetic material and paste the gene that codes for the protein that can be used as natural dye in the gap. The bacteria is allowed to multiply and divide; once a small colony is formed by consecutive division, they are inserted into a bioreactor containing nutrient solution and an air flow in which the cells increase further in number and begin producing the dye protein in abundance due to provided optimal conditions.

Temperature, pH, concentration of sugar/ nutrient are all monitored during this process. The dye is separated using chemical separation techniques and extracted through a pipe that leaves the bioreactor.

Within the following years, ambitious founders and scientists become aware and onboard with the dream of revolutionizing fashion to make it better for us and our planet. Due to this the inventions of engineered spider silk, fungi based materials and faux/ imitation leather arose.

These brands did not take the common path to becoming another brick in the wall of fashion, they started a movement- for the planet, for the future, for the people. By ensuring clothing can be in alignment with nature and ecosystems, they have reshaped the rejuvenation of fashion.

From lab to wardrobe to runway

While syn-bio can be used in technical fields such as engineering and biomechanics, the fashion industry’s growing need for sustainability amongst all the soon-to-be landfill stuffing demands a science-backed solution. Many companies are already underway revolutonizing the traditional apparel industry through sustainable, biodegradable fashion; designers blossomed wonders using biotic materials which are practical and don’t compromise on creativity.

Instead of using petrochemicals and polymers such as nylon and polyester, brands crafting fabric, dye and coloring through a process involving fermentation and a bacterial growth culture (read about synthetic production of proteins using bacterial cells in the SPLICED. article ‘Empire state of bacteria’).

Some companies that took the ‘one small step’ to a ‘giant leap’ for sustainable fashion:

1. Spiber, a Japanese biotechnology startup that makes ‘Brewed Protein’ utilizes the standard bio-fermenter method while partnering with manufacturers of sportswear and sweater brands, seeping into even more categories currently.

2. Huue, founded in Berkeley, California excels at making the world’s most sustainable dyes to be embedded into the production process of various industries- a major sector of them being clothing brands.

3. Colorifix is a biotechnology firm in England with a similar goal that uses DNA sequencing to create new custom organisms with the ability to grow dye for textiles specifically, aiming to significantly improve the fashion-waste problem.

4. Bolt Threads situated in Washington focuses on synthesizing bioengineered compounds for personal care products. They have also developed a way to transform mycelium (mushrooms) into eco-leather.

These companies are not just concocting eco-friendly wearables that look sparkling on the runway, they are changing the way the world the fashion industry and paving the path for the various other trademarks working towards a shared vision. Perhaps our wardrobes will be transformed into ones that leave a reduced imprint on the environment in the coming years.

A recent article by John Sterling published on SageJournals titled ‘Synthetic Biology Struts Down The Runway’ claims that “bio-based sustainable alternatives will be the new vogue”.

Biology is advancing and is shaping new norms; it is in our hands - the decision to choose the winding current path or the newfound ambitious one.

References

World’s first T-Rex leather product unveiled - a luxury handbag designed by Enfin Levé

Synthetic Biology Struts Down the Fashion Runway

Could synthetic biology lead to sustainable textile manufacturing?

The health impact of fast fashion: exploring toxic chemicals in clothing and textiles

How Can Bio Materials Reduce Fast Fashion Waste?

Beyond Fast Fashion: Embracing Natural Dyes for a Greener Future

When the first cacao beans in rainforests were being harvested by the South Americans - more specifically people from what is currently called Ecuador - the beans inside pods looked nothing like a delicacy. These plants that grow exclusively near the equator weren’t sweet at all; they were in fact bitter tasting. However, ancient people formulated cacao beans into delicious beverages. Yes! - chocolate began as a beverage in which cacao beans were mixed with spices of different varieties to make various flavors, usually savory.

Some sources also deduce that the drink was later used as medicine; hot chocolate gradually grew into a trend. Only reserved for the wealthy, hot chocolate came in multiple popular flavors including sweet and savory versions. Hot chocolate was like their coffee. Bars began to arise with the main product being hot chocolate.

Many other sources remain parallel with the story that combining ground cacao beans with sugar/ spices and milk was invented by a court jester to amaze their king who loved the combination so much that he declared chocolate to become an official high-class delicacy for people of high stature. None of the palace chefs were able to replicate the jester’s formula which lead to the court jester who was once detested by the emperor to be promoted for a lifetime. Again, these are just some versions of the real history.

When you think of chocolate houses, you imagine a fictional candyland where the clouds are made of cotton candy and trees produce gummy-candies. On the contrary chocolate houses - like coffee houses - grew in popularity as third spaces and trendy locations to meet and to network in the 17th and 18th centuries (1600-1700 AD).

In the following decades during the 18th century, cacao beans were not expensive and a luxury anymore- laymen would craft their own chocolate beverages at home. This increase in accessibility however further increased the public’s liking toward chocolate unlike normally when a trend becomes overused it usually dies out. Commercial production of sweet chocolate as solid bars by combining it with dairy and fats accelerated and people adored this advancement.

Today, chocolate is everywhere, in all forms and sizes- everybody knows what it is. It is found in general stores, eateries, bakeries, designer buffets etc. It is used in a plethora of desserts and incorporated into innumerable edible products such as ice-cream, cakes and more. Not only is it limited to food and desserts, chocolate as a concept is found in animated films, architecture, fashion design plus lots more creative fields. Festivals dedicated to chocolate are held globally - there is even an established world chocolate day.

We all love chocolate

But what actually happens when we consume it?

Studies conclude that consuming quality chocolate in mindful quantities can be beneficial to our health. The best kind is dark chocolate due to its higher cocoa content, lesser sugar and lesser lipids. When we ingest it, melting chocolate triggers our taste buds, sending a signal through sensory neurons to the brain informing it regarding the entrance of chocolate.

Chocolate contains compounds such as phenethylamine which stimulate neurotransmitters and induce release of chemicals such as serotonin as well as the release of endorphins. Neurotransmitters are chemicals produced by the brain upon an impulse from the nerves to signal the suitable response. They are the signals (mailmen) that travel in their vesicles (vehicles) through the network of nerves that make up the nervous system (roads).

Endorphins are the same tiny messengers that are generated when you exercise or participate in a challenging physical activity- they improve your mood, stabilize emotions and provide a sense of motivation and satisfaction.

Serotonin is the ‘happy’ chemical - known to boost your mood, increasing productivity and overall metabolic efficiency.

Theobromine is also an effect of chocolate consumption which enables greater mental alertness, reduces reaction time and ameliorates cognitive speed and function.

Polyphenols are something chocolate is rich in; they are also found in caffeine and help relax blood vessels, enabling a better blood flow. These reduce blood pressure since vessels become less constricted, improving circulation to the heart and the brain.

Flavanols are like the siblings of polyphenols with a talent that goes hand-in-hand with their brothers. They are known to improve endothelial vascular function while reducing the levels of bad cholesterol in the blood. They also encourage the growth of new blood vessels while contributing to neuroprotection by preventing neuro-degradation.

Antioxidants in the form of cocoa are present in chocolate that reduce free radicals and limit oxidative stress, protecting against cellular damage. (Free radicals are highly reactive and hence react with bodily cells by oxidizing them resulting in damage to the cell). This also helps deal with insulin sensitivity.

We are in fact wired to love chocolate

A few years ago I read a part of the book ‘Unstoppable Us — How Humans Took Over The World’ Volume 1 by Yuval Noah Harari. Curated for younger readers, the book explains human evolution through engaging storytelling and pictures. Many segments of the book have stuck with me till this date; one of them being where the author explains why humans have a ‘sweet-tooth’.

Although our fondness towards sweet tasting food has a deeper biological reasoning and lifestyle influence, this particular book views it from another angle - where sweets become necessary for survival.

My interpretation of it is: Long before we had mobile phones, online delivery and artificial intelligence - wait no even before we had kingdoms - perhaps during the stone age, humans were nomads.

‘Nomads’ originates from the Greek word ‘nomados’ which translates to wandering around in search of pasture. Humans lived as tribes that migrated occasionally from one place to another, taking everything with them. These location changes would not be less like one neighborhood to the next consecutive one and more like one state to the next; tribes/ communities would walk all day, everyday for numerous days till they find a location they saw fit.

Long hours of walking through forests, deserts and savannas where food is scarce obliged them to consume whatever nutrients they laid their eyes upon. The most commonly found edible during these stone age mega marathons were trees with fruit - fruit that naturally contained sugar - sweet fruit. Figs, apples, plums, mulberries, pomegranate.

Due to this limitation in cuisine, the nomadic people often developed a craving for the sweet fruit during the endless hours of walking (since that was the only food source available when their dried fruits ran out).

From fruit to bean to soul snack

The unabridged version of the biography of your chocolate bar:

1. Harvesting

   Ripened cacao pods are harvested by cutting them off from the tree then splitting them open to acquire the beans from the pulp.

2. Fermentation

   The beans in fruit form are transferred to boxes where they are covered in banana leaves for about 2-9 days allowing them to ferment while developing key flavor profiles.

3. Drying

   Fermented cacao beans are laid out and left to sun-dry for 1-2 weeks to ensure moisture levels are below 7% to prevent them from growing mold.

4. Roasting

   Dried beans are roasted to remove acidity, make them easier to peel and enhance their aroma.

5. Winnowing

   The roasted beans are cracked, and the outer shells are separated from the inner "nibs," which are the main ingredient in chocolate.

6. Grinding

   Nibs are ground into a liquid paste known as cocoa liquor, or cocoa mass.

7. Conching

   The chocolate is refined by a machine that mixes, agitates, and aerates it, often for several days, to smooth the texture and remove any remaining acidic flavors.

8. Flavoring

   Ingredients like sugar, cocoa butter and milk powder are added to the machine and are made to mix with the chocolate.

9. Tempering

   The mixture is heated and cooled to specific temperatures to stabilize the cocoa butter, ensuring a glossy finish and a firm snap.

10. Molding

    The tempered chocolate is transferred to molds and let dry. It is then packaged and ready to be shelved.

‘Cooking’ vs ‘Engineering’ chocolate

Synthetic biology is revolutionizing the chocolate manufacturing world, developing new ways and alternative processes during the production of our beloved dessert that focus on improving its sustainability, reduce its impact on the environment and lower time, costs and effort.

Chocolate manufacturing companies have been introduced a loophole in the recent years which allows them to cut back on costs while generating the same volume of product. This ‘loophole’ at times involves syn-bio and usage of alternative ingredients to avoid transportation and hassle of supplying from farmers.

The downside is farmers don’t get paid as much (since the need for some ingredients reduces).

Cocoa butter; a key component of modern chocolate bars is being replaced by engineered, high-value lipids (fats) made using modification of yeast cells’ DNA to improve the overall consistency for a cheaper cost.

How? - Yeast is a type of bacteria and hence its genetic material can be modified and manipulated to produce almost any protein/ fat that we program it to produce. This feature of yeast- although found in almost all bacteria- is the reason for many industries such as breadmaking and wine fermentation include yeast due to its availability.

The modified yeast cells are introduced into a fermenter where the nutrient-rich culture and controlled airflow allows the bacteria to multiply and increase in number; more cells that can produce the required protein arise. The contents of the fermenter are then extracted (some amount at a time not all at once to keep the culture growing) through a pipe connected to the fermenter. The needed protein/ fat is acquired through separation techniques and then purified etc.

Chocolate made entirely without using any cacao at all has been created. The fermenter process is used along with yeast to produce cocoa compounds exactly like the naturally found ones in laboratories instead of in farms to eliminate tree-grown cacao beans from the recipe. Most times it is easy to tell the difference between authentic and synthetic chocolate, but what happens when the gap becomes indistinguishable?

Dig deeper

Why I Talk About Chocolate (And What It Has to Do with the Future) - Dr. Tiffany Vora

The history of chocolate - Deanna Pucciarelli

The Secret History of Chocolate - National Geographic Kids

The History of Chocolate - English Heritage

The History of Chocolate | Where does Chocolate Come From? - Magnum

An echoscope is a remote operated vehicle with an optical sensor system used in a plethora of fields; in marine biology, this technology is used for observation of the microdistribution of marine life; in surgical procedures, it is guided through a fiber optic cable to map and visualize molecular and cellular activity.

The multifacetedness of this creation in collaboration with its caliber to help us conceptualize tiny biological structures with immense detail and control is why it is deemed a powerful medical tool and is the reason this intricate development is the title of a newly commencing series within SPLICED.

Echoscope will begin as an alternative segment of the weekly Saturday articles. In this series, SPLICED will feature interviews with researchers, professionals and scientists from a plethora of diverse biological backgrounds with unique and truly insightful stories to tell. The signature type of publications will all the same continue.

Overview on Parkinson’s Disease

10 Million people today live their lives impacted with Parkinson’s worldwide. Caused by nerve cell damage due to a significant dopamine drop, this disorder may not be fatal yet has significant implications on the lifestyle of an affected individual. Some symptoms include muscle tremors, rigidity in moving limbs which at times lead to paralysis. It can also be a result of environmental factors such as exposure to pesticides, head injury and more. As for now, there is no known cure to this disease however the symptoms can be controlled through treatment plans personalized to the patient’s specific circumstances and needs including medication, lifestyle changes and surgical procedures

Imani Elaine Porter

3rd Year Ph.D. Candidate in Stanford Biosciences Genetics Program

Most research on Parkinson’s starts in the lab — petri dishes, cell cultures, mouse models. Imani Porter starts with data. As a 3rd year PhD candidate at Stanford, she’s approaching the disease from a computational angle that’s never been tried before, looking for patters in biology that traditional methods would miss entirely. She also hosts the NALA (STEM) podcast, where she highlights topics such as career navigation or science communication and strives to make science feel like something that belongs to everyone.

Below is the interview in a (question) + (answer by the scientist) format:

1. If you had to explain your current research using only objects in a kitchen, how would you do it?

My current research is quite computational at the moment, so I am learning a lot of computational tools and methods used for multi-omics analysis (using different datasets such as human immune expression data and gut bacterial abundance data), and I’m interpreting a lot of this information in the context of Parkinson’s disease or PD in a way that has never been looked at before.

There have separately been many PD microbiome studies and immune expression studies. There has even been discussion on how the gut microbiome may regulate host response in this diseased state, but no one has looked at this directly. If they have, it was in other diseases that only have some overlap with the pathologies observed in PD.

If I were to use objects in the kitchen to describe the active process of what I’m doing, it’s like trying to understand the role of each ingredient of a sauce, when I’m given partial recipes of gravies, soups, and stews that share a few ingredients with my sauce.

2. What is one problem your work could potentially solve in 10 years?

Yet, the contribution of many scientists over many years collectively fills this bucket of knowledge. I’m hoping that within the next 10 years, my work will contribute to informing the approach of other Parkinson’s disease researchers in studying these patients. This could pertain to the types of data they collect and how it’s analysed; however, the longer-term goal is to better understand those with this condition so that they can be given more effective care and live happier, less debilitating lives.

3. Is there a moment in your research where you completely failed, and what did that failure actually teach you?

There are many moments in my research that I’ve failed at. There is so much learning in science, so every time I learned a new tool or new technique at the bench, I failed at least 2-3 times before having a successful go at it.

I’ve discarded the wrong part of a DNA extraction and had to collect a whole new sample; I spent 2 weeks accidentally killing hundreds of C. elegans by putting them in a higher dosage of treated media than I was supposed to; I’ve failed at crossing fruit flies and micro-dissections; I’ve failed at forming crystals for protein crystallography; I’ve failed many bacterial transformations; I even spent a whole summer failing 1 experiment during my first rotation of grad school.

There are many other examples of how I’ve failed during my time spent in this line of work, but each time, I was confronted with the same questions of, “why didn’t it work this time?”, “what could I have done better?”, “should I ask for help?”. Each time I went down my list of questions, I became hyper-vigilant about following the protocol closer, even writing more specific notes so I wouldn’t mess it up the next time. Also, when I asked for help, it gave me knowledge that I wouldn’t have been able to figure out on my own from people that became crucial mentors for my development and success as a scientist.

4. If you were 16 again, what is one biology-related skill you would start learning today?

If I was 16 again, one biology-related skill I would start to learn is not exclusively biology-related. It’s not even necessarily a skill but a practice. Learning to ask “stupid” questions was a recurring hurdle for me when I was younger. It was usually when a new concept was being introduced to me that I somehow felt I should immediately understand the topic at the same time I’m being exposed to it. Because of this, I became afraid that I was stupid if I didn’t understand something and internalized that if I had a question or didn’t understand something, it meant I was stupid.

This is something that I still struggle with today at times, and if anything, this practice got more difficult as I got older, because I felt that enough time had passed or I’ve been immersed in a topic long enough that I should know by now. I didn’t realize until later that this was all my misunderstanding of what learning and doing science was about.

Takeaways

Science and STEM are disciplines that are necessary to sustain life and ameliorate the quality of living. Science is about exploration, innovation and solving problems/ answering questions through investigation. This is why asking the questions- regardless of if they may be deemed ‘silly’ questions- is important because by asking questions we connect the dots in our thought processes which is what scientists strive to achieve.

A quote from this interview that will stick with me is “many of our individual contributions are only a drop in a bucket” which marvelously illustrates how all scientific research piece together as if they were to paint a segment of a much larger jigsaw puzzle. The end goal remains — to fill the bucket or to complete the puzzle which keep enlarging as it continues to develop. And although one singular piece of a puzzle cannot portray the full image, the surrounding pieces lay the foundation and help fill in the blanks, collectively orchestrating and aligning to present the big picture.

Acknowledgements

Thankyou to Imani Porter for her time and honesty - and for making a recipe analogy which was indeed memorable.

The NALA (STEM) Podcast:

NALA (STEM) Instagram page

Check out Imani's podcast

Dig deeper:

What is Parkinson’s Disease | Parkinson’s Foundation

The Parkinson’s You Don’t See: Cognitive and Non-motor Symptoms

Bacteria existed on our planet before cells that contained nucleus did. For this reason bacteria are considered prokaryotic organisms and do not consist of a nucleus; instead their genetic material floats freely in the cell’s cytoplasm. Recent findings such as CRISPR gene editing and genetic modification in general utilize the versatility of bacterial cell DNA and its ability to be conformed and modified specifically.

They are also unicellular, meaning they exist in the form of single cells making all bacterial cells microorganisms. Hence, these microscopic creatures can be found almost anywhere on the planet imaginable- some even sustain themselves in outer space.

Too small to be visible to us yet insanely versatile and powerful, bacteria have ventured to destinations that are unreachable to humans; the extreme depths of the Mariana Trench, inside volcanoes, in the hearts of geysers and in space. Alongside these adventurous locations, they exist on everyday objects- on all the surfaces we touch, food we consume and everywhere on us and inside our systems.

Bacteria are often introduced to us at an early age as the ‘bad germs’- on our hands before we wash them or on the escalator handrails in the mall. On the contrary, there are approximately five nonillion (five times ten raised to thirty) bacteria on Earth in total which includes the 30,000 species/ types already named and the thousands more which are estimated to exist; all these species are not ‘bad’ for us and majority of them might never come in contact with a human. The harmful bacteria are usually intercepted by white blood cells that make up our immune systems before they can multiply and cause significant harm.

In our bodies there are bacterial cells which are either good, neutral or bad for our health and wellbeing. Bacteria have genes that produce metabolites which affect our physiology.

There are 20,000 to 25,000 genes in our body that are our own. However, there are millions of microbe genes that outnumber our own and influence changes in how our bodily systems operate. This millions of genes from various kinds of bacteria and fungi that have their own genetic material make up our internal microbiome.

Our somatic microcosm

‘Somatic’ means ‘of the body’ or ‘bodily’ and refers to the body’s corporeal aspects excluding the mind, spirit and germ (reproductive) cells.

‘Microcosm’ implies a mini world which contains systems representing ones much alike the real world.

At this very moment, your gut contains 100 trillion microbes including about 300-500 types of bacteria.

Our gut microbiome is the sum of all genes from the bacteria and microorganisms inside the gut. Since these influential beings have genes to produce metabolites- as mentioned before- they hold the power to control so much and potentially help us. They also determine and control our emotions, weight, cognitive functioning and food choices. Reciprocally, we have the power to manage our internal microbiome by selecting our sleep, exercise and diet choices.

For example, gut bacteria and the immune system work hand-in-hand to fend off pathogens (disease causing microorganisms) and maintain immune defense.

The gut-brain axis

A common myth is that ‘digestion’ refers to the entire journey of food through our systems while the fact remains that digestion is the process by which food we intake is broken down and converted into usable nutrients by the body using chemical and physical processes. It takes place throughout the alimentary canal also known as the digestive tract. During digestion, large molecules are converted into absorbable nutrients while the digestive system is like a factory where the microbes are the workers.

Essential enzymes that our bodies cannot produce are secreted by gut bacteria which aid in the digestion of food mainly resulting in usable forms of vitamins B and K.

The brain monitors and modulates all gut activity.

All the orchestral collaboration between the brain and the gut is possible due to the gut-brain axis or the GBA. This is a bidirectional link allowing two-way communication between the brain which is part of the central nervous system (CNS) and the gut which is part of the enteric nervous system (ENS).

This unexpectedly strong connection between two nervous systems- one consisting of the brain and the spinal cord and another made up of all the motor neurons, sensory neurons and interneurons in our guts- connects the brain to the gastrointestinal tract and helps with the regulation of optimal bodily conditions (homeostasis)

Joined via the Vagus nerve, this bidirectional communication is supported by microbial metabolites released by beneficial gut bacteria which encourage neurotransmitters to take effect for immune modulation.

• Healthy gut bacteria promote the production of muramyl peptides which act as signals to the brain enabling quality sleep for the individual.

• The gut impacts our HPA axes which are the main producer and secretor of cortisol- the primary stress response hormone.

• 90% of all the body’s serotonin- the happy hormone- is secreted by the gut upon the brain’s command.

• Foods your brain likes evoke dopamine production which takes place in the gut almost instantaneously.

The commonly experienced downside to this interconnection is the indigestion or a stomachache caused when one experiences high levels of anxiety or stress.

Knockout mouse

Though the name reminds me of the popular arcade game ‘whack-a-mole’, the knockout mouse is a model or technique used in various fields- primarily genetic engineering where it originated from.

A simple outline of this method; replacing or eliminating a specific target gene from a mouse to understand the gene’s purpose and significance. This was first carried out in the laboratory using mice hence the name.

Although this may raise the obvious ethical concerns, mice are used in the laboratory to study gene expression through such models since we humans share about 85% of coding genes with them. Mice also offer a feasible cost and size, fast reproduction rates allowing observation of the genetic changes over multiple consecutive generations and a genome that we have fully mapped out and understood.

By removing specific genes, scientists can observe and understand its physical and behavioral implications producing guidelines to develop vital insight on diseases such as cancer, diabetes and neurodegenerative illnesses. Research indicates that individuals who suffer from neurodegenerative conditions or illnesses have a smaller variety of gut bacteria as compared to their neurotypical peers.

There is still much to discover about the capabilities of the GBA in treating cognitive conditions and disorders. Using the knockout mouse method, researchers strive to uncover cures revolving around the function of the gut-brain axis.

Therapeutic strategies to treat various diseases which are consequences of an unhealthy gut conditions include a conventional lifestyle alongside consumption of probiotic foods in moderation. These help safeguard our internal microbiome or our somatic microcosms that house millions of tiny organisms whose impact on us depends on the living environment our choices shape for them.

Summary

• Bacteria are versatile microorganisms found literally anywhere. Their DNA are perfect for genetic modifications due to no ethical restrictions.

• The internal microbiome is a world of millions of bacteria and fungi inside us- mainly in our guts.

• GBA (the gut-brain axis) interlinks the brain to the gastrointestinal tract for transmission of chemical signals that influence our metabolism.

• Our microbiome greatly affects bodily function and can be maintained through lifestyle choices.

• In the knockout mouse method, a particular gene is removed from mice to observe its function; this is used by professionals while developing therapies and cures.

References

Gut microbiome explained in simple words - Science ABC

What is the gut microbiome?- Washington Post

How Bacteria Rule Over Your Body- The Microbiome - Kurzgesagt

The Gut and Brain: A surprising connection - BrainFacts.org

Gut-Brain link- Brainbook

In 2012, American biochemist Jennifer Doudna alongside French microbiologist Emmanuelle Charpentier discovered the capabilities of bacterial DNA when it comes to genome editing. For this they had been honoured with a shared Nobel Prize of Chemistry in 2020, 8 years after their groundbreaking breakthrough in 2012. They showed how bacterial immune mechanisms can be reprogrammed to alter genes, making the cells produce the intended proteins whose code has been incorporated into their genetic material.

Based on a natural system present in many prokaryotes (unicellular organisms without a nucleus such as bacteria), gene editing is carried out using two elements; CRISPR regions in the cell’s genome and the enzyme Cas-9.

Their findings had driven other scientists globally to deduce how these systems in bacterial cells can be applied to human and animal cells allowing us to potentially rewrite our genetic code- something that had been purely random since the beginning of time which varied based on inheritance and environmental factors.

If the core differentiation factor amongst us all can be altered and changed with specificity and precision, this discovery unlocks an entire new world of possibilities that have proven to be advantageous time and time again however its misuse can lead to the branching of various problematic implications. Think of it somewhat like an all-powerful device from a sci-fi movie which leads to chaos when in the wrong hands.

The universal code

DNA is the universal genetic material present in all organisms. It is a double stranded molecule and comprises of nucleotides attached to a peptide backbone. The nucleotides are what make DNA variable and are what differentiate the genome of an apple to the one of a horse. The order of nucleotides on a single molecule of DNA is the base sequence which determines the protein that it codes for.

Base sequences consist of nucleotides. There are four main nucleotides- each commonly associated with the letter at the beginning of their name; A,T,C and G (Adenine, Thymine, Cytosine and Guanine). However in an RNA molecule, unlike in DNA, Thymine is replaced with the nucleotide base Uracil. DNA is composed of two strand of bases wound parallelly with the strands joined together due to the bases on each strand being complementary to the ones opposite them on the parallel strand. While Adenine is exclusively complementary to Thymine, Cytosine forms bonds with Guanine only.

DNA is double-stranded in the shape of a double helix. RNA is one strand of DNA.

Every strand of DNA or RNA has two ends labelled 5’ end and 3’ end (5-prime and 3-prime ends). These numbers correspond to the position of a functional group on the pentose sugar (sugar containing 5 carbon atoms in a ring) and determines the directionality of the molecule. Both are synthesized from 5’ to 3’ direction.

What is CRISPR exactly?

The term CRISPR is an acronym for ‘clustered, regularly interspaced, short, palindromic repeats’. It refers to segments of the genome in a prokaryotic cell which the description can adhere to.

Clustered- The segments are on one part of the genome in groups.

Regularly interspaced- Separated by base sequences of similar length in between them. These base sequences are known as ‘spacers’ as they are present in the spaces between the CRISPR segments.

Short- The number of individual base pairs in one segment ranges from 23 to 47.

Palindromic- Read the same sequence regardless of if it is read backwards or forwards. In reality they are not completely symmetrical, but the term CRISPR containing a ‘P’ was kept.

Repeats- The palindromic segments of the same base sequence repeat in the same part of the genome cluster.

One entire CRISPR unit comprises of a handful of the same palindromic short segments which are separated by spacers- each spacer is unique and not palindromic.

Role of the Cas-9 enzyme

This is an enzyme that operates collaboratively with pegRNA to form the CRISPR Cas-9 complex which is introduced into cells for replacement of a target sequence.

Having the ability to cut the genetic material as well as initiate synthesis of the new sequence of nucleotide bases, this enzyme is a crucial part of specific gene editing.

The molecular mechanism behind it all

The CRISPR Cas-9 system can be used to identify target sequences and edit them to change the outcome protein that forms from the genetic material.

One proven approach is using Prime editing guide RNA (pegRNA).

The structure of pegRNA is a version of RNA with additional attachments at both ends. At its 5’ end, it contains the guide sequence complementary to a palindromic repeat in the CRISPR unit and also contain the nucleotide bases that allow binding to the Cas-9 enzyme. At the 3’ end attached adjacently is a primer binding sequence along with an RT template (code complementary to the replacement sequence).

The pegRNA is now modified to:

• Bind to the Cas-9 enzyme

• Identify the CRISPR repeat

• Bind to a primer which initiates the replacement process

• Synthesize the replacement sequence using RT template

  Cas-9 undergoes two changes:

• Reverse transcriptase is attached to allow assembly of nucleotides complementary to the base sequence on the RT template to synthesize replacement sequence.

• Endonuclease in the enzyme is deactivated such that it is able to form a nick/ cut in one strand and not both.

The pegRNA and Cas-9 complex is inserted into a cell and begins gene editing:

1. Cas-9 moves along the DNA to locate the target strand using the complimentary bases of the target sequence on the 5’ end of the pegRNA.

2. Upon identification, a nick is made in the complementary strand on the target sequence. Due to the cut, the strand has a new 3’ end and a new 5’ end where the gap is formed.

3. The two strands of DNA become separated in that region and the guide RNA binds to the target sequence by complementary base pairing. This makes the site suitable for reverse transcription to occur (synthesizing of the replacement sequence).

4. Since the RT template containing nucleotides complementary to the replacement sequence is present, reverse transcription occurs forming a sequence one nucleotide at a time making a segment complementary to the RT template. This takes place in the 5’ to 3’ direction.

5. The target sequence which has now been replaced forms a single stranded flap since its place has been taken by the newly synthesized replacement sequence. The sequence opposite the replacement is not complementary to it since it was paired with the old base sequence. Both these are fixed by DNA repair enzymes. They modify the strand so the DNA is restored, removing the flap (old target sequence) and making the bases complementary to the replacement segment.

6. Finally, the DNA contains the replacement sequence and its complementary sequence opposite to it. The DNA will then function normally.

CRISPR Therapeutics

Diseases that can now be treated by gene alteration.

Sickle cell anemia: A mutation in the gene that codes for haemoglobin (a protein found in blood which produces its red color) results in the protein to be abnormal, making red blood cells sickle-shaped and rigid. It is difficult for blood cells of this shape to travel around the body due to extremely narrow openings of capillaries. Sickle-shaped blood cells hence get stuck in blood vessels posing a great risk. CRISPR Cas-9 has been used to treat this mutation by replacing it with the sequence that codes for a normal haemoglobin proteins.

Beta thallassemia: An inherited mutation that causes reduction in concentration of beta-haemoglobin in the blood plasma. Affected individuals have less to no beta-haemoglobin which leads to anemia and various symptoms such as jaundice or enlarged organs. Its previous treatment involved risky blood transfusions or iron chelation therapy to manage iron concentration. CRISPR Cas-9 complex targets the sequence that codes for beta haemoglobin to replace the mutated sequence with a new normal base code.

Problems

For the genetic modification system to work, it must be inserted into the tissue where the mutation or disease originated from. Due to this requirement, illnesses such as Cystic fibrosis which CRISPR has proven to remove in experiments are yet to be implemented since the mechanism is to be introduced into the affected individual’s lungs. The examples mentioned above of diseases that this system has proven to cure originate and affect cells in the bloodstream, hence the easy insertion of the gene editing mechanism to enable exposure to the target cells and target sequence.

This relatively new technology can be used for the modification of many target sequences not necessarily a disease causing code, hence it must be used ethically and only when required to prevent misuse leading to negative implications.

Summary

Discovered by Jenifer Doudna and Emmanuelle Charpentier in 2012, CRISPR Cas-9 is a system based on a mechanism naturally found in prokaryotes that allows modification of a target gene repeat sequence. It does so by identifying, cutting, reconstructing and replacing the target sequence in DNA of a cell which results in change in the functionality of the gene sequence. The mechanism involves pegRNA and the Cas-9 enzyme. Proven to treat various diseases, this technology can be advantageous yet some obstacles are yet to be solved.

In molecular biology, the term ‘spliced’ corresponds to a process during the post-transcriptional modification of the genomic sequence pre-mRNA which is ultimately conformed into a template for protein synthesis. Splicing allows the filtration of base sequences from post-transcriptional pre-mRNA, snipping off the segments of bases that are introns (interrupted codons) to enable the joining of all the exons (expressed codons) to form a new mRNA molecule, preparing it to be translated into a protein more efficiently. Basically, the sequence is edited by cutting out and rejoining the cut ends of necessary segments.

What is synthetic biology?

The discovery of synthetic biology unlocks a plethora of possibilities in the worlds of science, healthcare and development; in this field, living systems are redesigned to create sustainable products and solutions, programming them to serve a useful purpose obliging synthetic biology to become incorporated in multiple industries that embrace natural complexes to comprehend and modify for specialized applications.

The discoveries caused by syn-bio will evolve the way in which crops are cultivated, how meat is produced and the impact of biofuels as a sustainable alternative to traditional non-renewable fuels.

To understand better about what synthetic biology is, here are some examples of innovations it has driven us to produce:

1. CAR-T Cell therapy

A treatment developed by altering the mechanisms of the patient’s extracted helper-T cells (A type of white blood cell) has proven to combat blood cancers such as leukemia and lymphoma. After being programmed to identify the exact disease causing cells, the modified, multiplied cells from the patient’s own body are reintroduced into the blood; they target the cancer cells and have resulted in remission rates of 50% to 90%.

2. Cultured protein

An ethical alternative to standard livestock farming in which genuine meat is cultivated using animal tissue in controlled, laboratory environments. Due to genetic modification, the produced meat is often healthier and less prone to contain infections or mutations than if it was from a living animal. Usually, intensive livestock- the most common types of livestock which are maintained in unhygienic, high-stress conditions- are prone to carry harmful hormones or pathogens (disease causing organisms). Through cultured meat, protein goals can be satisfied without the risk of infection.

3. Engineered Spider silk

The silk produced by spiders to weave their webs can be an extremely useful, versatile material. Instead of farming spiders, bioengineered bacteria such as yeast is inserted with the code to form the spider silk protein. The bacterial cells are cultivated to obtain the strong industrial grade material which is biodegradable and biocompactable. Its fibres’ tensile strength can be compared to the one of Kevlar steel which combined with the silk’s ability to withstand high pressures when stretched makes it a crucial asset in the production of artificial tendons and advanced medical implants that are subject to stress. It is a naturally produced substance which unlike implants made of steel or polymer feels more organic and human.

Summary

• Synthetic biology is a branch of biotechnology that re-engineers organic systems to create useful solutions.

• CAR-T cell therapy programs cells produced by the patient to target blood cancer cells.

• Cultivated meat/ protein is lab grown meat which tastes the same, is ethical and significantly reduces the risk of disease

• Spider silk is produced using bacteria instead of spiders and is proven to be strong under tension, justifying its use in making artificial tendons.