Research Description

My main interest is to study biology at the level of its macromolecular machines and to gain a quantitative biophysical understanding of how these machines drive important cell biological processes. Since new tools enable new biology, I also develop advanced microscopy methods that aim to overcome the limitations of current methods and help us to visualize the macromolecular machineries of the cell in action with high spatiotemporal resolution.

Specifically, I am interested in the molecular machinery involved in two fundamental biological processes: transport machinery that drives intracellular trafficking of vesicles and transcriptional machinery that drives gene expression. At the heart of and common to both biological problems is the interaction of multiple proteins with each other and with other proteins to form functional macromolecular nanoscopic complexes. The spatial and temporal organization of these interactions is tightly regulated and the failure to form these macromolecular complexes in the right place and at the right time can have catastrophic consequences.

Studying the spatiotemporal organization and regulation of these macromolecular complexes necessitates non-invasive tools that can visualize them with high spatial and high temporal resolution. Single molecule imaging and in recent years the emergence of super-resolution microscopy have opened new doors to visualize the dynamic assembly and disassembly of macromolecular complexes in living cells. Over the recent years, my group has been pioneering major developments in the field of super-resolution microscopy (Balint et al, PNAS 2013, Durisic et al Nature Methods 2014, Tam et al PLoS One 2014, Cella-Zanacchi et al Nature Methods, 2017, Gomez-Garcia et al, PNAS, 2018). These methods have enabled us to gain novel insights into the transport of vesicles along their cytoskeletal tracks (Balint et al, PNAS, 2013, Verdeny et al, JCS, 2017, Mohan et al, JCB, 2019), the spatial organization of nucleosomes along the chromatin fiber (Ricci et al, Cell, Otterstrom et al, NAR, 2019, Gomez-Garcia et al, Cell Reports 2020) and the dynamics of chromatin-transcription factor interactions (Lerner et al, Molecular Cell 2020, Gomez-Garcia et al, Cell Reports, 2020). Importantly, we have taken a highly quantitative biophysical approach in studying these biological processes, going beyond qualitative descriptions towards precise quantitative models. For example, we have made important strides in quantifying the stoichiometry of macromolecular assemblies such as nucleosomes at nanoscale resolution (Durisic et al, J. Neuroscience 2012, Durisic et al Nature Methods, 2014, Ricci et al Cell, 2015, Cella-Zanacchi et al, Nature Methods, 2017, Cella-Zanacchi et al, Biophysical Journal, 2019).

Diversity & Inclusion Initiatives

• 2020- Co-director, Physiology Department Committee on Diversity and Inclusion
• 2017 – 2019 Philadelphia SPARK Outreach Program