Sofia Moraes, a PhD candidate in Biochemistry, Molecular Biology, and Biophysics (BMBB), was recently awarded a fellowship in the Howard Hughes Medical Institute (HHMI) Gilliam Program. Dr. Reuben Harris, who is a professor in BMBB and a HHMI Investigator, is her graduate mentor and also involved in the program.
This year’s cohort includes student-advisor pairs from 38 schools across the country. Pairs are selected based on the student’s research achievements and the advisor’s commitment to building a more inclusive scientific community. Students in the program identify with groups historically excluded or underrepresented in science. As supportive mentorship and an inclusive research community are key reasons PhD students stay in science, the program holds these as top priorities.
Mentorship and community at the core
For Moraes, the prospect of meeting and building relationships with both students and faculty across the country is a huge draw. “I’m eager to mill around a room with Nobel Laureates and get to know the person behind the science. I want to hear about their journey and obstacles they overcame along the way,” she says.
The opportunity to connect with fellow graduate students is also an exciting aspect to the program. Moraes is keen to learn from others about their experiences advancing diversity, equity, inclusion, and justice (DEIJ) efforts within their programs and fields.
This aspect of the training is also a critical component of faculty members' involvement. "I'm thrilled to help lead BMBB's DEIJ efforts, and HHMI Gilliam support will provide a vital boost to a cohort of graduate students, including Sofia, who are working to proactively engage CBS underrepresented minority students and help introduce them to supportive research labs as early as possible in their degrees,” says Harris.
A peek into the research
Moraes views DEIJ work and building community as key aspects of her training. She’s also driven by the research and piecing together experiments to reveal intricacies of protein interactions.
“I’m fascinated by basic research. It’s really important to have strong basic science so that the underlying knowledge is there when other researchers go to explore the medical or applied side of things,” says Moraes.
When it comes to warding off viral, bacterial and other infections, the human immune system has a diverse set of defenses. While many people are familiar with inflammation, antibodies and an increase in white blood cells, what happens inside an infected cell remains murkier. This is where the Harris Lab comes in.
They study a suite of proteins — known as APOBECs (pronounced ‘ape-oh-becks’) — that mutate DNA, including viral DNA. These mutations, depending on their context and frequency, can boost or harm human health. Some mutations dampen how effectively viruses can replicate, which can fight off viral infections. In other cases, they can negatively impact the cell’s own DNA and ultimately cause the development of cancers.
Lab members work on both the basic and the applied sides of the system. Some aim to better understand how APOBECs interact with different viruses and others work to develop novel therapeutics against viruses and cancer.
A “factory” gone awry
Moraes is drawn to the molecular aspect of the research. She’s interested in how related herpes viruses interact with APOBECs. She likens the system to a factory.
Herpes viruses replicate within the nucleus of a cell and from the virus’s standpoint, this is their “replication factory.” The virus has one goal: make as many copies of the virus as possible so it can go on to infect other cells. Any “cog” in machinery will make the virus less successful at replicating and ultimately less successful at infecting its host.
In recent years, members of the Harris lab found that APOBECs were acting as a “cog” in the viral replication machinery. From the cell’s perspective, it’s advantageous to stop a virus from replicating. From the virus’s perspective, it wants to remove any glitch in machinery and thus some produce proteins to knock out APOBECs.
This response found in a type of herpes virus that infects humans — and how it plays out across different viral types — fascinates Moraes. She’s focused on identifying viral proteins that interact with APOBECs during infection and understanding the strategies used by different viruses to protect themselves against APOBEC-mediated mutations. Working to better understand the molecular mechanisms behind interactions between APOBECs and other proteins in the nucleus has implications for virologists and cancer biologists.
The Gilliam Program will allow Moraes to make new connections that will no doubt have positive impacts on her research pursuits. “I’m excited to take the opportunity to rise into new leadership roles, both in research and in DEIJ work,” says Moraes. “Not only will the experience help bolster skills for the next steps in my career, but it will also boost my confidence.” —Claire Wilson