Bowdoin Science Journal

Noah Zuijderwijk

Daniel Kang in the Spotlight

by

“I give a lot of credit to my mentors, past and present, who have shown me how I should be thinking about unexpected results” – Daniel Kang

Some teachers care so deeply for what they teach, it is almost as if their passion osmotically transfers to their students. This was certainly the case for Daniel Kang when Mrs. Hahn ignited a water jug and propelled it from one end of his high school chemistry classroom to the other, or when she used ethanol to animate a fiery pumpkin for Halloween. Just like the jug and the pumpkin, Mrs. Hahn’s eyes lit up when she taught science. Her passion inspired Daniel to plot his own course toward becoming a scientist. Now, Daniel is a biochemistry major at Bowdoin College, where he works in Professor Dube’s lab as a senior researcher. Though Daniel is not lighting water jugs or pumpkins on fire, he is applying Ms. Hahn’s chemistry teachings to his research project on sugar pathways in bacteria.

When I asked Daniel why he focuses on sugars, he explained that bacteria need them to survive. It turns out, glucose, sucrose and fructose – the simple sugars with familiar names – are not alone under the sugar umbrella; there are over 700 sugar “species”. Bacteria absorb the simple ones as building blocks and synthesize more complicated chains of sugar called glycans. They place these glycans on their membranes, which allows them to evade our immune system and invade our bodies.

In the lab, Daniel adds fluorescent tags to the simple sugars bacteria absorb. Then, he cuts bacteria up into parts to see where fluorescent sugars end up and in what amounts. This allows him to map out sugar transport throughout the bacteria. With that information, scientists in pursuit of new antibiotics might develop mechanisms to disrupt sugar movement. For example, if we know the mechanisms behind glycan synthesis, we may be able to prevent bacteria from producing the complex sugar molecules they need to hide from our immune system.

 
 
 
 
 

“Eventually I hope to become a physician scientist – to both attend to patients, and contribute to science”

 

 
 
 
 
 
 

Through his project, Daniel is learning what it means to be flexible in the face of unexpected results. For example, a couple weeks ago, he ran an experiment to determine whether lower temperatures would slow down sugar transport. Given that coldness slows down molecular processes, he expected sugar transport to be slower as well. Instead, he observed the opposite; under colder conditions, sugar transport sped up. While reflecting, Daniel admitted these kinds of results are confusing. Yet, he tries to see the unexpected as a moment of reflection and redirection. With experience, he hopes to become more patient and open to identifying new approaches to problems as they arise.

“I love to be productive and do things fast. But in research, it is better to be the tortoise than the hare.”

Philip Spyrou in the Spotlight

by

“The lab and the art studio are fundamentally the same space; you have a material, a question you want to answer, and you experiment” – Philip Spyrou

Give a teen unfettered access to the internet and they might transform into a brain-rotten screenager. Luckily, in Philip Spyrou’s case, hours spent looking at Reddit feeds and YouTube videos did not translate into cognitive decline. In fact, quite the opposite was true; he used his internet privileges to teach himself how to cultivate life. As a high school sophomore, Philip experimented with hydroponics and tried to grow mushrooms using soil he made with whole grains and a pressure cooker. His resourceful and creative fascination with life led him to a chemistry and visual arts double major at Bowdoin College. He now studies the role of proteins in neuron function as a senior researcher in Professor Henderson’s chemistry lab.

When Philip showed me around the Henderson lab, he explained that proteins play a near-infinite number of crucial roles in biological processes. One such process is the formation of synapses in the brain. In simple terms, a synapsis is the coming together of two neurons to exchange information – a crucial mechanism for routine brain function. However, neurons need the ability to “crawl” around brain tissue before they can find other neurons and form synapses. SRGAP proteins enable neurons to develop finger-like protrusions from the cell membrane with which they can “crawl”. Philip studies how the membrane attracts these proteins.

Though one might think studying neurons requires a lab furnished with preserved brains in glass jars, Philip’s research (disappointingly) does not involve Frankensteinian techniques. In fact, Philip works with model cells called Giant Unilamellar Vesicles (GUVs), which are artificial membrane systems used to study cell functions. By modifying the GUV’s membrane, he observes how different membrane compositions attract SRGAP proteins. These observations can then be mapped onto neurons to understand how they develop the ability to “crawl” through brain tissue.
 

To study this neuron crawling mechanism, Philip has to think beyond the two dimensions of a textbook. After all, a protein’s three-dimensional structure is key to its function. In this regard, his time in the art studio has proven valuable to his work in the lab. Philip believes the lab and the studio aren’t all that different, and that working with clay and ceramics has trained him on how to gather materials, ask questions, and design experiments with a three-dimensional mindset.

 
 

“I like thinking visually, structurally, and three-dimensionally about the biological processes I study”

 

 
 
 

The three-dimensionality of Philip’s research unfolds at the molecular scale. It requires him to spend most of his time thinking about intangible processes. But, he says, it helps him to think of the applications of his research. For example, loss of proteins that enable neuron cells to crawl around the brain might be implicated in cognitive disabilities and memory loss. This is something he hopes to continue researching by earning a PhD with the goal of eventually becoming a full-time researcher.

As Philip continues on this path toward becoming a scientist, he finds it important to keep reminding himself of where his passion for science comes from. His love for understanding life originated in his backyard when he figured out how to grow plants and mushrooms. Though he does not foresee himself going back to researching those forms of life any time soon, he does want to keep tapping in to his fifteen-year-old self’s creative fascination for life.

Gracie Scheve in the Spotlight

by

“To do research, you have to be stubborn. But also, don’t be too hard on yourself” – Gracie Scheve

Around 600 million years ago, marine invertebrates emerged as Earth’s first multicellular organisms. Today, Gracie Scheve is scheming to make a career out of researching their extraordinary life cycles. Her interest in invertebrate evolution and development has not come out of the blue though. Gracie’s family would drive down from their home in Cincinnati, Ohio to Florida every summer for vacation when she was little. There, she would load buckets onto her paddle board, paddle out to sea, and collect countless jellyfish. Back on shore, she would spend hours marveling at her catch. Now, years later, Gracie has carved out her niche in invertebrate biology as a senior researcher in the Rogalski lab at Bowdoin College. With Professor Rogalski, she investigates reproductive strategies of Daphnia, or the common water flea.

In late Spring, Gracie brought me along to her study lake. While she collected water samples, Gracie explained that Daphnia are cyclical parthenogens. In simple terms, they can reproduce both sexually and asexually. Typically, their wild population is exclusively female. This all-female population reproduces asexually into the next generation of clonal daughters with every reproduction cycle. In Gracie’s words “Daphnia are girl bosses”. However, things change when they encounter stress. For example, disease can trigger Daphnia to produce males with which the females will sexually reproduce. This, in turn, results in more genetic diversity, which increases the population’s stress tolerance and survival probability. Through her research, Gracie hopes to gain more clarity on what stresses alter reproductive behavior, and by what mechanism.

Over the summer of 2024, Gracie observed an unexpected pattern in the field; the only stress factor that seemed related to an uptick in sexual reproduction was a novel fungal parasite. Though this might mean Gracie and Professor Rogalski will get to name a new genus of fungus, for now, it is leading to more questions than answers. For example, how does the fungus affect Daphnia? And is it truly inducing sexual reproduction, or was Gracie’s observation merely coincidental? Gracie is currently experimenting with this fungus in the lab. She admitted that she might not find the answers before the end of her senior year. However, she is excited about the novelty of her research.
 

“I want to go into a field where there are questions I am interested in that haven’t been answered yet”

 

 
 

Along with asking new questions comes a level of uncertainty that makes Gracie’s research unpredictable. It means that over the past months, Gracie has experienced many unexpected turns, like when all Daphnia had disappeared in mid-June. She recognizes these surprises are a natural part of research and that it is a good thing she is learning how to handle them now – especially because she hopes to take her next step into an evolutionary biology PhD program. Her undergraduate research experiences have taught her not only to be flexible, but also that research requires an underappreciated range of soft skills. Whereas quantitative skills and book smarts seem to prevail, Gracie shared that having an open mind, being persistent, and being patient with oneself are some of the most important qualities of a researcher. Wherever Gracie will go next, she will take these lessons with her.

“Fieldwork is frustrating sometimes because you’re not in control. And when you do have control in the lab, results might not map onto the field at all. Regardless, you have to be patient with yourself and your research.”

Yasemin Altug in the Spotlight

by

“I am delirious in lab. You have to be to have fun” – Yasemin Altug

When she was 12 years old, Yasemin cared little for popular book series like Percy Jackson or Harry Potter. Instead, she read Beyin Nasıl Çalışır? – How Does the Brain Work? in Turkish – before going to sleep. At that age, her mom said she was a “special child”. As the years passed, her interest in neuroscience only grew. Now, Yasemin is an undergraduate senior researcher in Bowdoin College’s Powell lab where she studies the lobster cardiac nervous system (hence the red lab coat).

On a late September morning, Yasemin invited me into the lab. As she gathered ice to numb the lobster, she explained that small fluctuations in temperature can disrupt crucial functions mediated by the lobster’s nervous system, like breathing and pumping blood. Whereas our warm-blooded bodies can regulate our body temperature, cold-blooded creatures, like lobsters, are at the whim of their environments.

In the Gulf of Maine, that environment is heating up as a result of global warming and shifting currents. To understand how the lobster’s cardiac nervous system responds, Yasemin investigates how, or even if a specific heart-modulating hormone is involved in warming compensation. To do so, she measures the lobster’s heartbeat at various temperatures in the presence and absence of the hormone. When cardiac neurons are active, they leave behind identifiable signatures in the heartbeat force signal on the cardiogram. Yasemin can use these signatures to derive whether the hormone is affecting activity in specific cardiac neurons, and if warming conditions change those hormone-neuron interactions. She can then use that information to construct a more complete picture of ocean warming effects on lobsters.

To conduct her experiments, Yasemin has to pay the cost of a living organism as she collects the lobster from its tank, numbs it, dissects it, and cannulates its heart. This meticulous work comes with feelings of discomfort and guilt. To overcome those feelings, she focuses on how her studies might help the lives of people living in Maine. In this state, a string of lobster-dependent communities lines the coast. Lobsters hold ecological, cultural, and economic value to these communities. After all, tourists do not come to Maine for its chicken sandwiches. Therefore, warming oceans pose a threat not only to Maine’s coastal ecosystem, but also its culture and to people’s livelihoods. The relevance of her research in all these contexts makes it worth the effort.

 

 

“I have to do what I have to do for the net positive outcomes of research. I think this is more important than my discomfort.”

 

 

Beyond the moral dilemma of working with living creatures, Yasemin also shared that it has been particularly difficult to navigate academia in her second language. On top of that, she comes from a place where some people – especially women – are not always given opportunities to enter STEM fields. During her time in classes at Bowdoin, she saw other students express themselves fluently, get better grades, and achieve better dissections in lab. It triggered her imposter syndrome. But the curiosity and drive of that little girl who used to read Beyin Nasıl Çalışır? before bed never left her. Yasemin realized that the skills often socially expected of women – like being a good listener, working with people, and problem solving – are the most important skills in the lab. Her message to other women in STEM is to not count themselves out:

“Being a good scientist is not about understanding the concepts with ease, it’s not about being perfect, it’s about being able to deal with mishaps… because scientists don’t care if you know how to hold a pipet, they care if you can learn how to hold a pipet.”

Microscopic X-men Survive Thousands More X-rays Than Humans

by

New study finds novel protein linked to water bears’ extreme radiation resistance with applications to cancer treatment.

Water bears, or tardigrades, are microscopic creatures with eight legs. They are so hardy, Stan Lee may very well have drawn inspiration from them while writing X-men. What they lack in telekinesis, invisibility, and shapeshifting, they make up for in resilience to extreme temperatures, high pressures, vacuum environments, dehydration, starvation, and DNA-damaging ionizing radiation (IR). To put things into perspective: Humans can tolerate at most 5 grays (unit of radiation), while tardigrades can survive upwards of 4,000 grays. The exact mechanisms behind their IR resistance remain unclear, prompting researchers to investigate their genetic code in hopes of uncovering insights that could benefit human health.

When IR comes in contact with DNA, it can cut through one or both strands of the DNA double helix structure, leaving behind single or double-stranded breaks. To prevent genomic instability and cell death, some genes encode proteins that form mini shields against IR, while others encode corrective proteins involved in repair mechanisms after IR damage. A team of researchers at Paris-Saclay university in Orsay, France found that human and tardigrade cells sustain similar damage after IR exposure, but that human cells died, whereas tardigrade cells did not. This suggests humans and tardigrades have similar preventative strategies, but only tardigrades are equipped with the repair mechanisms needed to recover.

To explore the possible genes involved in these repair mechanisms, the researchers used a technique called transcriptomics on three species of tardigrades. With this technique, they sequenced RNA from cells of the three species after IR exposure. The sequences told the researchers which genes were turned on in response to IR, and how those differed among the three species. They found upregulated expression of numerous previously described DNA repair genes across all three species. However, one gene – also shared across the three species – stood out in particular. When examining its RNA sequence, the researchers realized they had encountered the code to a novel protein. They called it TDR1, or Tardigrade Damage Response 1.

The exact role TDR1 plays in DNA repair is unclear. Nevertheless, observations of TDR1 aggregates in tardigrade cells suggest TDR1 might be involved in a DNA condensation mechanism. In other words, when DNA experiences breakage from IR, TDR1 proteins mobilize to change the DNA’s three-dimensional structure into a densely packed cellular space around the breakage. This structural change introduces DNA pockets where crucial repair enzymes are more likely to come in contact with broken DNA segments. This way, TDR1 helps restore the DNA’s structural integrity.

Besides merely describing TDR1, the researchers also sought to understand whether TDR1 protein could be applied to human cells. They found that, when expressed in human cells, the TDR1 gene also helped our cells recover from IR damage. This advance in understanding IR resistance could have immediate applications to cancer treatment because today’s methods still often rely on heavy doses of ionizing radiation. IR does not only cut through the cancer cells’ DNA, it cuts through all the healthy cells caught in its crosshairs as well. Therefore, with the development of new IR resistance tools, we may be able to reduce the side effects resulting from healthy cell damage after radiation therapy.

Sources:

Dall’Agnese, G., Dall’Agnese, A., Banani, S. F., Codrich, M., Matilde Clarissa Malfatti, Giulia Antoniali, & Tell, G. (2023). Role of condensates in modulating DNA repair pathways and its implication for chemoresistance. Journal of Biological Chemistry, 299(6), 104800–104800. https://doi.org/10.1016/j.jbc.2023.104800

M. Anoud, E. Delagoutte, Q. Helleu, Brion, A., E. Duvernois-Berthet, M. As, Marques, X., K. Lamribet, C. Senamaud, L. Jourdren, A. Adrait, Heinrich, S., G. Toutirais, S. Hamlaoui, G. Gropplero, Giovannini, I., L. Ponger, M. Gèze, C. Blugeon, & Coute, Y. (2024). Comparative transcriptomics reveal a novel tardigrade specific DNA binding protein induced in response to ionizing radiation. PubMed Central, 13:RP92621. https://doi.org/10.7554/elife.92621

Cover image credit: “Mikrofoto.de-Baertierchen3” by Frank Fox at http://www.mikro-foto.de/ is licensed under CC BY-SA 3.0 Germany.

Gut Viruses Might Be the Key to Life Saving Early Pancreatic Cancer Diagnosis

by

New study links the community of viruses in our gut to early pancreatic cancer development – a potentially lifesaving discovery.

With a mortality-to-incidence ratio of over 90%, pancreatic cancer (PC) is among the most deadly forms of cancer. Since its early stages often bear no distinct symptoms, the disease grows stealthily until it’s too late. What’s more? Scientists foresee a near 100% increase in PC deaths, from 466 000 in 2020 to over 800 000 by 2040. To avert this grim future, researchers strive to develop methods for earlier detection, and subsequent earlier treatment. A 2022 study at the University of Tokyo linked PC to changes in gut microbiome composition. This has directed gastroenterologists’ focus to the microbiome in the search for new diagnostic tools.

The gut microbiome is often understood as the community of bacteria living in symbiosis with our digestive tract. Bacteria, like E. coli, break down our food in exchange for a safe habitat. However, bacteria do not aid our digestion for brownie points. As evolving creatures, they constantly test the limits of our gut ecosystems. As far as we understand, that’s where viruses come in; they regulate the bacterial population in our guts. The microbiome, therefore, consists of not only bacteria but also viruses. All viruses together make up our body’s virome.

An imbalance of bacteria and viruses has previously been observed in PC patients and is believed to be a factor in PC development. For example, the bacterium Roseburia intestinalis is significantly less abundant in the guts of PC patients compared to healthy individuals. This particular bacterium produces a cancer-inhibiting metabolite called butyrate, a substance that limits cancer development by suppressing inflammation and reducing the expression of genes involved in tumor cell growth. Other bacteria produce cancer promoting-metabolites, like lipopolysaccharide (LPS). This substance activates our immune system in the presence of pathogens, but also stimulates inflammation, and therefore, promotes cancer growth in the process. The balance of bacteria producing these two kinds of metabolites depends on the virome’s composition. Therefore, if we could identify the gut viruses causing imbalances, we might be able to diagnose patients earlier.

Researchers at Xi’an Jiaotong University took on this hypothesis when they performed a study that compared PC patient viromes to those of healthy individuals. They sequenced the DNA of 183 fecal samples from a Spanish and a German cohort with 101 PC patients and 82 healthy individuals. After sequencing the samples, they filtered out human DNA by comparing the sequenced DNA to an established human reference genome. They then used viral references to compare viral DNA from the samples to known viruses. After statistical analyses confirmed significant difference between the PC patient group and the healthy group, they identified which viruses were present in the PC patients’ guts, and how those differed from the ones found in healthy individuals. As pancreatic cancer severity increased, virome diversity decreased in PC patients. Additionally, the viruses present in the affected individuals targeted different bacteria compared to the gut viruses found in healthy individuals, offering a potential explanation for the relationship between unbalanced microbiomes and cancer growth.

Using their results, the researchers created models to differentiate PC patients from healthy individuals. These models succeeded with 87.9% accuracy. Though these findings do not offer the ultimate solution to late PC diagnoses, access to virome information could be used as a diagnostic tool in addition to the tools currently available. Namely, a viral DNA sequencing-based tool could identify the specific viral biomarkers linked to pancreatic cancer. In the future, at risk groups for PC might, therefore, be asked to supply fecal samples for gut virus analysis during routine check-ups. In the case that PC-linked biomarkers show up, these at-risk groups could be provided early treatment, potentially saving their lives.

Sources:

Miyabayashi, K., Ijichi, H., & Fujishiro, M. (2022). The Role of the Microbiome in Pancreatic Cancer. Cancers, 14(18), 4479. https://doi.org/10.3390/cancers14184479  

Zhang, P., Shi, H., Guo, R., Li, L., Guo, X., Yang, H., Chang, D., Cheng, Y., Zhao, G., Li, S., Zhong, Q., Zhang, H., Zhao, P., Fu, C., Song, Y., Yang, L., Wang, Y., Zhang, Y., Jiang, J., & Wang, T. (2024). Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer. Journal of Medical Virology, 96(7). https://doi.org/10.1002/jmv.29809

Cover image by magicmine, https://stock.adobe.com/search?k=pancreas+cancer&asset_id=343535067