Biophysical Society Bulletin | April 2023

Biophysicist in Profile

Jerelle Joseph Area of Research Multiscale computer simulation approaches for understand ing and engineering biomolecular condensates

Institution Princeton University

At-a-Glance

Jerelle Joseph , Assistant Professor of Chemical and Biological Engineering at Princeton University, grew up in Dominica, a Caribbean island nation. After taking to science at a young age, she pursued higher education at the University of the West Indies followed by the University of Cambridge. Now, Joseph’s group is focused on understanding and engineering intracellular compartments—specif ically biomolecular condensates—through the development of quantitative multiscale computer models.

Jerelle Joseph

Jerelle Joseph grew up in Dominica, an island nation in the Caribbean Sea. Her mother worked as a nurse and her father was a jack-of-all-trades, with jobs including teacher, shopkeeper, politician, and fisherman. Joseph describes her parents as very intelligent and gifted people who had few op portunities, especially where higher education was concerned. “Importantly, they both placed a huge emphasis on education and stressed that my sisters and I did well at school. My fa ther pushed us to become independent, critical thinkers,” she shares. “For instance, although he was more than able to help us with our schoolwork, he rarely did. He would encourage us to ‘read a book’ and figure it out ourselves. My mom was very supportive of our academic development; I often recall during my exam period she would stay up late at night with me while I studied.” For the last two years of secondary school, students in the Caribbean choose the subjects that they will study for the Caribbean Examination Council exam, and Joseph was encour aged to study science. “Physics was my favorite science sub ject, particularly because my first physics teacher was amaz ing at explaining challenging concepts,” she says. “In college I fell in love with chemistry due to two fantastic chemistry teachers.” She was the first in her immediate family to attend university, enrolling at the University of the West Indies (UWI), Cave Hill Campus, Barbados to study chemistry and mathe matics. “For my undergraduate thesis, I decided to do a theo retical chemistry project with Professor Sean McDowell at the UWI. It turned out to be an excellent fit for me,” Joseph states. “We were using quantum mechanical approaches to study a special type of noncovalent interaction—halogen bonding.” After completing her bachelor’s degree, she stayed on to work on a master’s degree with McDowell. “During my [master’s degree studies] I grew interested in bio-related research topics, and so when the time came to decide what I would read for a PhD, I gravitated towards projects on proteins,” she recalls. She attended the University of Cambridge for her PhD,

in the group of David Wales as a Gates Cambridge Scholar. “My PhD work was focused on studying protein folding. Specifical ly, I studied intrinsically disordered proteins and proteins that undergo large-scale structural rearrangements (metamorphic proteins). The conformational space of these types of proteins are traditionally difficult to explore via classical simulation approaches. I, therefore, developed computational biophysics techniques—within the potential energy landscape frame work—to interrogate these systems,” she explains. For her postdoctoral studies, she worked in the group of Rosana Collepardo-Guevara and as a research fellow at King’s College, Cambridge. “I studied how intracellular compart ments arise via phase separation. In contrast to organelles such as the nucleus and mitochondria that are enclosed by membranes, the most widespread compartments inside cells completely lack physical membranes. These compartments, often referred to as biomolecular condensates, are thought to be formed and sustained via the physical chemistry of phase separation, analogous to oil droplets in water,” Joseph describes. “While the idea of phase separation inside cells is transformative, there are several open questions as it relates to the mechanistic details of this process in the context of spatiotemporal organization within cells. During my post doctoral studies, I developed multiscale computer simulation approaches to elucidate the physicochemical underpinnings of phase separation inside cells and to characterize biomolec ular condensates.” Joseph started her new position as an assistant professor in chemical and biological engineering at Princeton University in January 2023. “The Joseph Group’s research focuses on understanding and engineering intracellular compartments (specifically biomolecular condensates), through the devel opment of quantitative multiscale computer models,” she explains. “Particularly, we are interested in the structural and dynamic characterizing protein–RNA compartments: probing how these compartments form under periods of stress, how

April 2023

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