Irina Serysheva

Cell function depends on the continuous flow of molecules into and out of the cell and between intracellular compartments. Understanding the structural basis of ion transport is one of the most important frontiers in structural biology. Ion channels, a class of integral membranes proteins, control this process, and play critical roles in a wide array of cellular and physiological processes including muscle contraction, brain functions, fertilization, hormone secretion, gene transcription, metabolic regulation, immune responses and apoptosis. The research in our laboratory broadly focuses on the area of structure-function of ion channels with specific emphasis on Ca2+ channels. Dysfunction of Ca2+ channels has been implicated in abnormal intracellular Ca2+ levels associated with many pathological conditions such as Alzheimer’s, Parkinson’s and Huntington’s diseases, autoimmune diseases, AIDS, cancer and stroke. The Serysheva lab has established itself at the forefront of single-particle cryo-EM of ion channels. Her group has solved 3D structures of ryanodine and inositol 1,4,5-trisphosphate receptors, also known as Ca2+ release channels, at intermediate resolutions which remain the highest resolution structures of these ion channels to date. Dr. Serysheva has pioneered novel vitrification protocols for integral membrane proteins in a near-native environment. Given recent technological advancements in the cryo-EM field, current efforts in the Serysheva laboratory focus on achieving near-atomic resolution structures of Ca2+ channels such that the Ca backbone and the side chains of the protein can be determined. With this structural information in hand, she anticipates to decipher the function of these ion channels and their relation to multiple neurodegenerative and muscle diseases. These findings will be essential for the rationale used for the design of therapeutics targeting Ca2+ channel in disease.