BME Seminar Series: Melike Lakadamyali, PhD, University of Virginia
Zoom Password: 231428
Melike Lakadamyali, PhD
Department of Physiology
University of Pennsylvania
"Super-resolution imaging of chromatin organization in health and disease"
Super-resolution microscopy has been playing an instrumental role in providing new insights into how the genome is folded and packaged inside intact nuclei in single cells. I will present our work on using super-resolution microscopy to visualize and quantify the spatial organization of chromatin with nanoscale spatial resolution in single cells. Our work has revealed that at the nucleosomal level chromatin is a disordered fiber composed of groups of nucleosomes packaged at varying densities, which we named nucleosome clutches. Despite the heterogeneity of nucleosome clutch organization, the size and packing density of nucleosome clutches is cell-type specific and correlates with cell fate. Our recent results also show that nucleosome clutches and chromatin nano-structure can be remodeled via chemo-mechanical cues. In particular degenerative chemo-mechanical cues during disease lead to aberrant chromatin nano-structure and loss of mechano-epigenetic memory, potentially leading to alterations in cell phenotype.
Dr. Lakadamyali received exemplary training from Prof. Xiaowei Zhuang and Jeff Lichtman at Harvard University. In 2010 she joined the Institute of Photonic Sciences (ICFO) in Barcelona as an Assistant Professor and was promoted to Associate Professor with tenure in 2015. She relocated to the University of Pennsylvania, Perelman School of Medicine as an Assistant Professor in 2017, where she is now an Associate Professor with tenure.
The overarching goal of the Lakadamyali lab is to understand the molecular mechanisms that regulate sub-cellular organization and the significance of this organization on cell function. Cells are highly compartmentalized: the sub-cellular positioning of organelles, nucleic acids and proteins are spatially and temporally coordinated to ensure that biochemical reactions take place at the right place and time. Dr. Lakadamyali’s program has three major focus areas that seek to advance our understanding of sub-cellular organization. In the context of the cytosol, she seeks to determine how the microtubule cytoskeleton and motors regulate transport and positioning of organelles within the cytoplasm and the functional consequences of disrupting proper organelle organization. In addition, she is interested in understanding how the molecular identity of organelles is linked to their spatial positioning and function. In the context of the nucleus, she seeks to understand how the spatial organization of chromatin regulates gene activity in health and disease. To address these key biological questions her lab takes an innovative approach of combining cell biological tools with advanced and highly quantitative microscopy tools including single molecule tracking and super-resolution microscopy. These research areas combined with our innovative approach integrate synergistically to move forward our understanding of how sub-cellular organization emerges and impacts cell physiology and pathology. Dr. Lakadamyali’s work has been funded by the European Research Council (ERC-Starting grant), NIH and NSF.