Chandrasekhar Hall

Bending by binding: How protein organization remodels the structure of membranes and genomes?

Ramakrishnan Natesan

University of Pennsylvania

Drawing from our recent works, in this seminar, I will present two different aspects of how
protein binding spontaneously reorganizes the structure of biological systems. In the first
part, I will focus on the computational aspects of studying structure formation in cell
membranes by the cooperative action of curvature remodelling proteins [1]. I will present an
overview of our multiscale computational method to study the thermodynamics of shape
transitions in cell membranes and demonstrate the predictive nature of our modelling using
the example of membrane tubulation by the action of ENTH domain containing proteins.

In the second part, I will focus on an informatics driven integrative approach to study the role of chromatin structure in cell function. I will present evidence from the analysis of nextgeneration sequencing data, specifically RNA-seq, ChIP-seq, and Exome-seq,
and demonstrate how enhanced binding of androgen receptor, a key transcription factor in
prostate cells, modulate the structure of the prostate genome. I will also discuss how
chromatin reorganization leads to drug resistance mediated solely by the epigenetic state and
the three-dimensional structure of the genome [2].

References
[1] Ramakrishnan, N., Bradley, R. P., Tourdot, R. W., & Radhakrishnan, R. (2018).
Biophysics of membrane curvature remodeling at molecular and mesoscopic lengthscales.
Journal of Physics: Condensed Matter, 30(27), 273001.
[2] Ramakrishnan, N., Rasool, R. U., Deng, Q., Aras, S., Lal, P., Sander Effron, S., et al.
(2019). CDK7 inhibition suppresses Castration-Resistant Prostate Cancer through MED1
inactivation. Cancer Discov, CD–19–0189.