In our cutting-edge structural biology lab, we harness the power of advanced cryo-electron microscopy and cryo-electron tomography to unravel the mysteries of the molecular world. Our focus is on dissecting the intricate behavior of membrane-bound proteins within their natural cellular environments and probing their responses to a wide array of stimuli at the atomic level. As part of Penn’s Institute of Structural Biology, we are at the forefront of addressing fundamental biological questions. Our research not only deepens our understanding of physiological processes but also paves the way for groundbreaking therapeutic innovations. Together with our peers, we are dedicated to pushing the boundaries of science and transforming our grasp of biology into tangible, real-world applications.

Our research focuses on understanding the structure and function of Transient Receptor Potential (TRP) channels, which play crucial roles in various cellular processes, including pain sensation, neuronal development, cardiovascular and renal pathophysiology, and cancer. The Moiseenkova-Bell laboratory is currently engaged in two primary areas of research. First, we aim to elucidate the structural basis for TRP channel activation, inhibition, and desensitization mechanisms through the application of cryo electron microscopy (cryo EM). Second, we seek to investigate how TRP channels regulate cellular functions and the implications of their dysregulation in human disease

Through this research, we aim to provide valuable insights into the role of TRP channels in health and disease, contributing to the advancement of both scientific knowledge and therapeutic strategies.

Single-Particle Analysis & Cryo Electron Microscopy

We are interested in investigating the atomic-level structure of membrane-bound proteins through advanced techniques such as cryo-electron microscopy (cryo EM) and single particle analysis (SPA). This approach enables us to reveal critical details regarding protein activation mechanisms in response to various stimuli. TRP channels, with their intricate network of physiological and chemical signals, can be effectively studied at this resolution to elucidate their precise responses. Our research specifically focuses on employing cryo-EM and SPA to uncover how these proteins interact with their native lipid environments, respond to physiological changes during sample freezing, and engage with a range of ligands, including small molecules and interacting proteins.

Cryo Electron Tomography

We are engaged in the direct visualization of membrane proteins and membrane-associated protein complexes within their native cellular environments using the cutting-edge imaging technique of cryo focused ion beam scanning electron microscopy and cryo electron tomography (cryo-ET). This method provides unparalleled insights into the spatial organization and interactions of membrane proteins, bridging the gap between molecular biology and structural biology while offering a more comprehensive view of cellular processes. Our research focuses on employing cryoET to uncover the presence and organization of membrane proteins and associated complexes on isolated organelles and in situ, aiming to enhance our understanding of how these proteins arrange within their native membrane environments.

Functional Studies of TRP Channels

We aim to unravel the complex functions and protein-protein interactions of TRP channels through quantitative mass spectrometry, a powerful tool that provides detailed insights into the dynamic proteomic environment. Additionally, we measure calcium flux and conduct patch clamp electrophysiology to assess the functional responses of TRP channels. These approaches, combined with other fundamental cell biology assays, enable us to uncover the molecular intricacies of TRP channels and understand how their proteomic landscape shifts in response to various stimuli. Understanding these interactions at the molecular level is crucial for deciphering the physiological roles of TRP channels and their implications for health and disease.