Perturb to understand: optical and thermal control of signaling and cell behaviour

MRC Protein Phosphorylation and Ubiquitylation Seminar

19 September 2024 1200hrs

Small Lecture Theatre, Medical Sciences Institute, SLS

Host: Ralitsa Madsen

Perturb to understand: optical and thermal control of signaling and cell behavior

Abstract:

The Bugaj Lab engineers precision tools to control intracellular biochemistry using light or temperature as inputs, with a focus on protein condensation, cell signaling, and cancer biology. I will first detail our recent work on new protein modules that respond to small changes in temperature, allowing dynamic, remote control of cell behavior both in culture but also deep within animal tissues. I will then describe how we apply these and other tools to understand the role of protein condensation in cancer signaling, with a focus on receptor tyrosine kinase fusions in lung cancer. I will detail our findings of how a diverse set of oncogenic condensates share similar interactions with host signaling machinery that may prime cells for survival and resistance during targeted therapy.

Bio:

Lukasz Bugaj is an assistant professor of Bioengineering at Penn. The Bugaj lab develops molecular probes to understand how signaling regulates cell behavior through time and space. The lab has deep expertise in optogenetic proteins, for example ones that cluster or undergo conformational changes in response to blue light, allowing control of a broad array of intracellular biochemistry in live cells. Recently the group has engineered analogous methods for thermal control of proteins, enabling precise, on-demand control of cells in optically dense settings like animal tissue. The lab then combines optical or thermal probes with advanced microscopy to study signal regulation in cancer cells and their response to therapy, as well as in understanding cellular stress response. Additional themes include a focus on the role of protein condensation and signal dynamics.  The Bugaj lab is primarily funded by the NIGMS MIRA, NSF CAREER, and the American Cancer Society.