Identifying Molecular Signatures

It isn’t often that a student has a clear idea of the path they will take to pursue their goals before entering college; for many, it can take years to figure out what they are passionate about. Edridge D’Souza is an exception. Edridge, a senior in the Honors College majoring in biochemistry and molecular biology and minoring in mathematics, envisioned himself doing almost exactly what he is doing now even before starting at UMass Amherst.

“I figured that I would join the biochemistry department, work in a research lab, do a thesis, and then apply to grad school,” he says. So far, Edridge’s route has followed this vision closely, starting with his choice of major. “[Biochemistry] gives me the best combination of all the major aspects that are involved in science research,” Edridge explains. “I want to stay on the molecular side of science research, and it also gives me a good background in chemistry, pharma, and even a bit of physics.” 

Edridge says that he first learned about the Honors Thesis process when he was entering the university. “As far as I knew, it just meant a big project that you had to write up in your senior year.” He notes that he didn’t have much of an idea of what his thesis was going to be about at the time. However, working in his lab as a freshman and sophomore, during which time his role was to support the research projects of upperclassmen, gave him a chance to “figure out how to do science research well” before embarking on his own project. 

After having several semesters to gain experience and formulate his own unique research question, Edridge arrived at his current work. The project, titled “GA- Repeats on mammalian X chromosomes support Ohno's hypothesis of dosage compensation by transcriptional upregulation,” is based in genomics and has involved looking at the human genome. In doing so, Edridge and his collaborators have identified a molecular signature for what is potentially a mechanism of a phenomenon known as “dosage compensation.” 

Edridge explains that “Dosage compensation is: males generally have one X [chromosome], females generally have two X [chromosomes]. How do we make sure that equal amounts of stuff is getting made even though they have a different number of chromosomes? That’s what’s called dosage compensation.” In the context of his research, Edridge and his lab members have come across one explanation as to why dosage compensation occurs in humans. 

Prior to pursuing this research, Edridge spent time during the summer doing similar work at UMass Medical School, preparing him to take on his own independent project. He also credits bioinformatics classes, taken with professors Jeff Blanchard and Courtney Babbitt, for giving him insight into the work that he has done in the lab. 

Aside from these mentors, Edridge had two faculty sponsors: Professor Michele Markstein, a biology professor who heads the lab and is Edridge’s principal investigator (PI), and Dr. Li-Jun Ma from the biochemistry department. “I picked [Dr. Li-Jun Ma] because I spoke to one of my biochemistry professors … and they told me to speak to Dr. Ma because she had experience in bioinformatics, and bioinformatics is heavily featured in this project,” Edridge says. In this way, Dr. Ma’s knowledge of the methods being used for the research have made her an invaluable asset to the team. 

Edridge explains that prior to beginning his research project, Professor Markstein was collaborating on a project with a colleague, Professor Erica Larschan of Brown University. 

“Erica Larschan is an expert in the subject of dosage compensation in fruit flies, and she was responsible for discovering this pattern of GA- repeats,” Edridge says. “Just for the fun of it, my PI was using this search program that we’ve developed in our lab that allows you to search genomes very quickly, and what she found was that by taking that signature ‘GA-GA’ sequence and searching for it in humans too, they found a similar pattern to what they saw in flies, which is that it’s way more common on the X-chromosome. We think that could show that the same GA- repeats might be doing the same thing in both flies and humans. That’s why we ended up naming this project ‘Lady GAGA: They Were Just Born This Way.’”

This humorous pop-culture reference is just the cherry on the cake; when asked about the potential impacts of this discovery on the world of genomics and beyond, Edridge says, “In the most ambitious sense, if we publish our results and they get attention in the scientific community, it could change a fundamental aspect of how we understand sex-linked traits in humans.” 

Edridge likens genomics research to looking at the stars in the sky. “They’ve always been there,” he notes. “Anyone who wants to look at them can look at them, but it was Brahe and Kepler who took the telescope, knew where to look in the right direction, and knew which right measurements to take, and that’s what eventually helped them figure out how physics works.” 

With regard to his research, Edridge says, “The thing about this project is that the work is already done. The human genome has existed for almost the past two decades now. What I like about this area of research is that it’s very much about finding things that are hiding in plain sight.” 

When asked about his motivations for pursuing this specific research project, Edridge explains that he enjoys the problem-solving side of the process and figuring out which questions to ask in order to find these hidden patterns. “They can be right in front of you; just because we’ve had the human genome for twenty years doesn’t mean that we knew how to cure every genetic disease. It takes a little bit of luck, a little bit of insight just to know where to be looking in the first place.” 

Edridge reflects on the experience of completing his Honors Thesis, noting that it has reinforced his future plans to continue working in the field of bioinformatics and genomics. “[My Honors Thesis] will basically have been thesis number one, and then next year, I’ll be doing another self-contained thesis project. It’s good to get that experience of having your own project, following through on it, wrapping it up, and presenting your findings,” Edridge explains. His advice for anyone pursuing a thesis project is to keep in mind that the process can be quite challenging. “You’re going to be drowning in experiments to run or work to do, but it’s really more of a marathon than a sprint,” he advises. 

As a 2019 recipient of the prestigious Churchill Scholarship, Edridge will receive funding to pursue a research-based master’s degree abroad at Cambridge University in the U.K. When he returns to the U.S., Edridge plans to apply for doctoral programs in order to continue his research.

Edridge’s time at UMass has shown him “a lot about who can do science, and that’s something that’s very much overlooked. Dr. Markstein has always been very good at emphasizing diversity, and what I think I’ve realized is that there’s no ‘smart gene.’ There’s no one type of person who’s going to be good at biology; instead, a good scientist is one who knows how to think critically, who knows how to ask questions. Historically, that’s been blocked off to a lot of people who haven’t had opportunity, who haven’t had access, but I think working at UMass Amherst and working in my lab has shown me how wide the selection of people who can do great, meaningful science is.”