Because Misaki Foster and I have been friends since we met last fall, I was bound to know something about her research before the chalk talk. While I knew she was working on mitosis in caterpillars, I didn’t fully understand her research until her chalk talk. I’ve always seen her passion for science, but to see her in action giving her talk blew me away! In addition to her passion and effective explanations, Misaki’s research in the Nijhout lab caught my attention.
When she said she worked with imaginal discs, I became even more excited about her research. I had seen them under the microscope in some of my first larval fly dissections, and they caught my attention as the spiral structures fluoresced red. In fact, I hadn’t heard of them before that moment when I asked Dr. Sherwood what they were. However, when Misaki mentioned that she was dissecting imaginal discs, I put together that these are a common structure among larval insects. Imaginal discs are small structures that begin inside the larva and emerge as a part of metamorphosis to become external structures. In fruit flies, there are multiple imaginal discs that will transform into the eye/ antennae, the legs, the wings, and more. Misaki studies the discs in caterpillars that will later become butterfly wings!
She explained how her lab studies development from the imaginal disc to the wing, asking the question, how is organismal growth regulated? To answer this question, she is measuring how much mitosis is happening in the wing at a given stage of larval development! While it makes sense that mitosis would directly relate to development, it’s something I had never thought about in that way. Once she dissects, fixes, and dyes the disc, she looks at it under a microscope to score each instance of mitosis. Misaki uses the chromosome positioning to identify cells in which mitosis is occurring, watching out for the different phases, like anaphase. Once she has these numbers, she puts them into a program that identifies hotspot regions of mitosis, and this is how they will find areas that are growing the most during different stages! The idea of mapping out mitosis is a new concept for me, but it’s one I find intriguing.
While Misaki’s project introduced me to new concepts, her explanations were logical and her presentation was amazing. As someone who uses flies as model organisms and sees the value of understanding larval development, I find Misaki’s project exciting and can’t wait to see where it leads!
While my research occurs in a lab, it was very interesting to learn of our other peers’ research that happens in the field. I was particularly fascinated by Xitlali’s project and its intersection in the broader efforts of environmental nonprofits.
Xitlali’s project looks at the effects of urban development on the environment, by studying biodiversity in different areas of watersheds by their level of developed land. New Hope Creek’s watershed, located within Duke Forest, is barely developed, whereas Ellerbe Creek’s watershed is located in a highly developed area. The level of biodiversity between these two differing locations is thought to be affected by urban development, and its role in facilitating the drainage of storm surge. Rainwater is able to slowly drain into New Hope Creek following a storm surge because it is rich in soil, while Ellerbe Creek receives rainwater at high rates because of pipes and drainage infrastructure. The timing of these processes is thought to affect the biodiversity of the two creeks. The hypothesis is that New Hope Creek will likely have more biodiversity due to its soil-rich watershed, in comparison to Ellerbe Creek. This will be measured by looking at different species of aquatic insects in the watersheds. Insects are also thought to be better able to stay on rocks on New Hope Creek. However, there are thought to be more “resilient” species in Ellerbe Creek, to withstand harsher water upheaval.
It was great to witness the huge range of interests within BSURF, and Xitlali’s, in many ways, felt like a huge contrast to mine (minus the bugs). I could not imagine having to go out to rivers to do my work! Moreover, while many of our projects have clinical applications or contribute to tool-building, Xitlali’s has great implications for studying the effects of neighborhood and class divides, a topic I would normally study outside of my realm of biology courses. While I must admit ecology has never been a major interest of mine within biology, I found this chalk talk super interesting, and I can’t wait to see where this project goes!
This week I wanted to take the time to shout out the work being done by George in the Mooney Lab! George’s talk stood out to me for two different reasons. The first is the fact that he gets to perform bird surgery this summer (wow) and the second is the potential impact on the field of neurobiology.
The fact that George performs surgery on zebra finches is mind-boggling to me. For context, I work with single-celled budding yeast (nowhere near a whole bird). When I need yeast for an experiment, I take a colony and inoculate a tube. When I need to dispose of a yeast culture, I spray some bleach. When I want to tag a protein, I can use PCR and an antibiotic plasmid. Due to the ease of growing them as well as their highly conserved metabolic pathways, yeast are wonderful model organisms for understanding molecular biology. In turn, zebra finches are a wonderful model organism for the Mooney Lab, which works primarily to understand neural mechanisms behind language. That being said, performing surgery on a living bird and then having to “sack” that bird is in a whole other league to spraying bleach in a flask. It is crazy how different our days in the lab look!
Now, onto the project. To summarize, George’s project is to test whether a new technology, dubbed Tech X, is functional in the dopaminergic neuron cells of zebra finches. The specific mechanisms of Tech X are unknown to me (for proprietary reasons of course), but what George divulged was that Tech X binds to specific RNA and fluoresces using green fluorescent protein (GFP). What’s so cool about this is that (if it works) Tech X will allow neurobiologists to make specific neurons fluoresce and therefore study them! Another part of George’s talk that I found interesting was that he’ll be targeting dopaminergic neuron cells. Dopaminergic cells, as the name suggests, make the neurotransmitter dopamine! For the Mooney Lab, dopamine is important because of its role in the language pathways of zebra finches. Beyond language however, dopamine’s most famous role is in that of reward. Drugs, from caffeine to cocaine, act in the mesolimbic pathway to essentially prolong the time dopamine is in the synapse of the neurons in the nucleus accumbens. Hopefully, the success of Tech X in making dopaminergic neurons fluoresce will reach beyond language and into other important avenues of neuroscience!
This goes without saying, but the brain is an incredibly complex organ to study. Developing technologies like Tech X help neurobiologists further understand how cellular interactions form complex networks that enable us to think, regulate our bodies’ metabolism, and perceive the world. Neurobiology is so so cool (at least I think so) so I really enjoyed hearing the many neurobiology talks this week!
At the Bursac lab, Anuj is working on engineering muscle cells by differentiating human iPSCs (as well as primary cells) into cardiac and skeletal tissue. These cells generate forces that model actual human tissue, which is pretty cool! In one of our core BME classes, we did a lot of work with muscle cells, action potentials, various muscle models (i.e Hill’s model), and a myriad of other things related to the work of Bursac lab. What gets me the most, though, is that this is Tissue Engineering. Can you imagine scientists growing an arm for you (well, not really, but really)? Vasculature, muscle, skin grafts, and even organs can be replicated! You name it (cue Thanksgiving grandma song)!
Anuj will also look into co-culturing endothelial cells & skeletal tissue together to better model human tissue. Another side project will study the use of Apelin 13, a peptide expressed largely in the heart, liver, and kidneys, and may have an angiogenic effect on vasculature. The lab is studying Apelin 13’s impact on endothelial and muscle cells, as well as its role on the cardiovascular system. Of course, the Engineer says that they liked an Engineer’s presentation the most! I mean, he speaks my language…To take second place, James Zheng’s research on the antiviral lectin GriffiThsin’s role in recognizing the spike proteins on the COVID-19 virus takes the cake for me. He’s also an Engineer. Maybe I listen harder to those who endure the struggles of P-reqs? Nonetheless, it was a great joy to listen to everyone’s chalk talk and find out more about their research. I’ll look forward to the poster presentations!
During his summer with BSURF, Zach is working with the McClay lab (which actually shares a space with the Wray Lab where I am working this summer). Dr. McClay is known for dedicating his career to mapping the gene regulatory network (GRN) of the model organism sea urchins. GRNs are very complex, specific, and intricate; many genes may be influencing the expression of one gene, and one gene may be influencing the expression of many genes. Zach is taking up a small part of the sea urchin embryo GRN, specifically looking at the gene Astacin-4, expressed in immune cells in the sea urchin. Very little is known about Astacin-4, but Zach is dedicated towards figuring it out – asking questions such as what genes are upstream, what genes are downstream, when it is activated, how long it takes to become activated, and what its primary function is. What is known about Astacin-4 is that it is expressed in cells known as blastocoels, located on the left side of the early developing sea urchin embryo. Establishing a GRN is a long and tedious process that includes continuously conducting a protocol known as in situ hybridizations. In simple terms, in-situs are conducted by throwing a cocktail of antibodies and G markers together with the developing embryo to see where and when Astacin-4 is expressed. By manipulating the system through gene inhibition or upregulation, the GRN of Astacin-4 can slowly be uncovered and mapped. Once the GRN for Astacin-4 has been defined, it may have applications in all types of other organisms, such as humans.
I knew going into the chalk talks that Misa Foster’s would be one to look forward to. From our previous conversations, I knew she was studying butterfly wing development. But even with my high expectations, she still managed to wow and amaze me, not only at her skill in speaking, but at the objective coolness of her research. Though it will be nowhere near as fascinating as her talk, I would like to relate to you all why I was so astounded and fascinated.
Misa is working in the Nijhout Lab studying the developmental biology of caterpillars, specifically their wing development. Biology 101 says creatures grow by cell division. Yet, while this is true, it doesn’t capture the whole picture. If cells were just to divide randomly in every direction, then every living thing would be a circle or a sphere. And yet, as evidenced in the magnificent beauty and architectural design of the butterfly wing, we know this is not the case. So, how do cells know when and where to divide? It is this fundamental question of developmental biology that Misa is trying to help answer.
To do so, she is extracting the imaginal disks (the precursor of the fully developed butterfly wing) from knocked out caterpillars. After staining these disks, she has to manually note and mark every mitosis event occurring in the cells. Then, with a little bit of programming, she can actually analyze where major trends of mitosis are happening in the wing. This addresses the “where” of cell division. By looking at disks in various stages of development, she can study the “when” by seeing how those spatial patterns of division change over developmental time. In addition, she can stain the wings with a different chemical to highlight DNA synthesis and see how this relates to mitosis patterns. Then, with a different program, she can map the patterns of DNA synthesis in the disks and see how they relate to mitosis trends at various stages of wing development. In total, this allows Misa to elucidate how cells grow and spread during wing development, unlocking another piece of the puzzle of how single cells can grow and develop into beautifully designed pieces of living art!
All in all, this is pretty cool! Misa is doing great work in developing our understanding of developmental biology and she did an outstanding job on Thursday presenting this radical science to all of us. Keep chugging along, Misa!!!
For those of us working on developing next-generation therapies, biotechnology, and pharmaceuticals, it’s easy to take the actual mechanism of drug delivery for granted. While the molecules we purify and test against pathogens and/or tumors may do perform quite well on a cell culture plate, ensuring that the actual administration and delivery of these drugs goes smoothly in live tissue is just as important. That’s what makes Camila’s work on pharmacokinetics at the Chilkoti lab so important.
Traditionally, when a drug is administered to the body, it has very little time to do what it needs to do before it gets excreted. This leads to multiple doses of highly-concentrated drug being used, which can yield additional negative side effects. A drug delivery mechanism that allows for more sustained, controlled release could substantially mitigate these challenges.
The Chilkoti group does a considerable amount of work on so-called elastin-like polypeptides, or ELPs. Derived from naturally-occurring elastin, these proteins undergo significant temperature-based solubility changes, becoming insoluble at body temperature and forming a slow-dissolving deposit within the target tissue. Any drugs attached to the ELP would then have much more time to act, resulting in sustained chemical release.
One of the biggest obstacles to the systematic usage of lectins like griffithsin as antivirals has been their high inherent toxicity in tissue. Given the strides being made by Camila and her colleagues in the Chilkoti lab, we may soon have the means to control just how much lectin gets released at one time, mitigating the adverse effects that would otherwise occur. I thoroughly enjoyed learning about her research and found her presentation of such a complex topic (just count the syllables in pharmacokinetics) super clear and interesting. Keep doing great things, Camila!
This week everyone in BSURF gave quick presentations to the rest of the program, essentially summarizing our work so far this summer in our respective labs. Specifically, I wanted to highlight Ben Johns’ chalk talk about his work on the cell-cell interactions underlying collective cell migration in the Hoffman lab. Ben’s research focuses on a protein called “vinculin,” which basically forms part of a larger scaffold connecting the actin cytoskeletons of neighboring cells, allowing them to coordinate their individual movements into a larger-scale phenomenon called “collective cell migration,” or CCM for short. With a palpable and contagious excitement, Ben explained to us how CCM is an integral part of essential processes like wound healing (regeneration) and morphogenesis, plus how his work in elucidating the localization and function of vinculin can enhance our understanding of CCM in general. This research particularly stuck out to me since my research this summer also focuses on development (albeit in sea urchins) and I find the whole field of regeneration fascinating, but hadn’t explored much how mechanobiology might play a role in either of these systems. He drew me in further, though, when he offhandedly mentioned the presence of alpha-catenin in CCM, because earlier this week my mentor had mentioned the role of beta-catenin in initiating movement during a developmental process our lab studies, and it was listed as a central element in the GRNs our lab has helped construct over the years. During the break after his presentation, we got to talking and found some pretty great connections between our work that might’ve gone undiscovered had Ben never mentioned it.
While these connections between Ben’s work and my own struck me as incredibly unexpected at the time, I’ve since come to realize they’re completely natural and, in fact, fully expected. It can be easy to fall into a rigid mindset sometimes, where you feel like you’re studying this specific field and nothing else, but Ben’s presentation reminded me of the intrinsic harmony across biological research. His project focuses on protein-protein interactions and a much more mechanical/physical model than the transcriptional GRNs of my work, and yet we’ve found this commonality where mechanobiology plays a role in development, and developmental GRNs play a role in operating and creating mechanical systems. Further, this symbiosis between our research interests has helped us both begin to understand each other’s fields of research better, which could alter the way each of us conducts research and think about problems that are archetypal to each of our fields which may require interdisciplinary solutions. Overall, Ben’s presentation helped energize me to continue looking into research that may just seem cool, if not completely unrelated to anything I’m working on, because sometimes that’s where the best and most valuable connections lie. Ben’s contagious enthusiasm for his work in mechanobiology, combined with these unexpected but awesome insights into our shared interests, meant that his presentation was a particular highlight of my week, and not one I’ll soon forget.