Interdisciplinary PhD program in Structural and Computational Biology and Quantitative Biosciences

Coyle, Weeks Join Biochemistry to Investigate Molecular Machines, Proteome

Although cells may seem endlessly complicated, at the end of the day they are machines that aren’t so different from those in daily life — like a Roomba used to vacuum a house. They are just millions of times smaller, made from different components such as proteins, and powered by chemistry rather than electricity.

It’s understanding these cells and the even smaller molecular machines inside them that drive the research of Scott Coyle and Amy Weeks, the two newest assistant professors to join the University of Wisconsin–Madison Department of Biochemistry in September 2019.

Coyle joins the department from a postdoctoral position at Stanford University and scientific consultant for a company he co-founded called CellDesignLabs. Before coming to UW–Madison, Weeks was a postdoctoral scholar at the University of California, San Francisco.

Photo of Amy Weeks
Amy Weeks

Weeks’ research is focused on developing tools to map the dynamic proteome. While the more commonly known “genome” describes the collection of all of the genes encoded in human DNA, the “proteome” is the set of proteins encoded in the genes present in a cell at any given time. Unlike the static genome, the proteome is dynamic and tricky to characterize.

“We often think of one gene as encoding one protein, but the reality is much more complex,” she explains. “After proteins are made, they can be modified in many different ways that impact their functions, so a big challenge following the completion of the human genome project is to define the ways in which the proteins encoded by each gene are modified and what the biological consequences are. We are tackling this question by engineering enzymatic tools that enable us to capture specific protein forms to identify them and to probe their functions.”

These modifications to proteins allow cells to respond rapidly to changes in their environment and errors in these processes often lead to disease. Understanding the proteome and mapping these modifications can not only provide basic insights into their function but help scientists look for new drug targets, for example.

Her interest in the proteome and enzymes — one of the tools she uses to study the proteome — began during her undergraduate at MIT and continued during her Ph.D. at the University of California, Berkeley, where she studied how an unusual soil bacterium synthesizes natural products.

“I find enzymes endlessly interesting, and I think it’s even more exciting when we can build from their functions to develop tools that can advance our understanding of biology,” she says. “The tools that my group is developing will enable us to identify disease-associated modifications that we can potentially target with drugs. They will also help us to understand whether certain protein modifications could serve as biomarkers of disease states.”

Photo of Scott Coyle
Scott Coyle

On campus she will be part of the Department of Biochemistry and Integrated Program in Biochemistry (IPiB), the joint graduate program between Biochemistry and the Department of Biomolecular Chemistry. She’ll also be a trainer for the Biophysics graduate program. In terms of teaching, she says her core values are integrating research and education, equipping students with tools for success, and creating an inclusive learning environment.

“The UW–Madison campus itself always seems to be buzzing with incredible energy, and I’m also a big believer in accessible public higher education so I’m excited to contribute,” Weeks says. “I hope that the outcomes of my research will influence and improve human health by advancing our basic biological understanding, which fits in with the Wisconsin Idea.”

Coyle is also interested in the inner-workings of the cell but is focused on the microscale machinery of cells and how it’s organized and controlled by nanoscale molecular components. He’s excited to see how that knowledge can be used to engineer new cellular and molecular machines with novel uses.

By gathering data on a complex system like a cell and breaking it up into smaller parts, he is able to see how different types of cells are “different designs assembled from a common toolbox,” Coyle explains. This kind of understanding can lead to insights for basic biology but also for disease states of cells with usefulness in medicine, agriculture, and other areas.

A unicellular hunter, known as Lacrymaria olor, in the act of striking and capturing its prey. Cells like these are one of many remarkable “microscopic robots” that Coyle studies to understand how nanoscale biochemical components can be organized and controlled to produce sophisticated microscale molecular machines. Image by Coyle.

“Although these behaviors may seem very complex, if we collect information about everything that the cell is doing over time, then we can start to find patterns in that data that teach us about the ‘programs’ that are driving the behaviors,” he says. “This is a highly interdisciplinary challenge that requires thinking about biological, chemical, and molecular systems on many different scales and figuring out ways to make connections between different fields.”

Understanding these “programs” is the first step in being able to engineer cells and molecular machines with novel functions, such as detecting disease in the human body or sensing chemicals in the environment. It’s something Coyle says he fell in love with while getting his undergraduate degree at Berkeley and continued in his Ph.D. at UCSF.

“I became fascinated with the fact that everything in biology, even me, is somehow just a consequence of biochemistry,” he says. “This fascination has motivated me to push myself to connect biochemistry to different scales at every stage of my career, such as applying this understanding to engineer new cell behaviors in immune cells at CellDesignLabs, which was acquired by Gilead in 2017.”

Coyle will be part of the Department of Biochemistry and IPiB. Through his teaching he hopes to instill foundational knowledge but also educate students on the latest developments in areas such as coding and machine learning. He also enjoys incorporating real-world examples into class lectures, he says.

“I was blown away by how absolutely outstanding a university UW–Madison is and how good a fit it is for my research interests and the program I’d like to develop,” Coyle says. “The biochemistry department has an amazing history and is full of incredible scientists — both senior and junior — who are earnest and genuine about helping new faculty achieve great science and education.”