Our genome represents Gigabytes of information that rest on a physical material known as chromatin. Throughout the lifetime of the cell, this information is copied, corrected, and modified by complex molecular assemblies that have evolved to interact with the chromatin via highly intricate mechanisms. In the context of all this activity, the fundamental task of the chromatin is to protect the delicate DNA polymer. The regulatory hub for these duties is a disc-shaped nucleoprotein known as the nucleosome, the smallest repeating architectural unit of chromatin.
The nucleosome is composed of approximately 150 base pairs of nucleic acid that are wrapped around four pairs of highly conserved proteins known as histones. Covalent modifications in the histones and the surrounding nucleic acid alter also the physical properties of the nucleosomes, which in turn, influence their interactions with chromatin factors. Some nucleosomes become more flexible such that their DNA is loose whereas others become more rigid such that their DNA is less accessible. Some other nucleosomes are decorated with electrostatic charges and novel functional groups that invite the assembly and action of transcription factors, chromatin remodelers, and modifier enzymes.
This diversity of nucleosomes introduces an additional layer of genetic information, i.e., the epigenetic code, and the exploitation of biophysical processes in the expression and inheritance of the epigenetic code invites a quantitative approach for their study.
The goal in our group is to elucidate the biophysical processes that influence the regulation of gene expression and inheritance at the molecular level. We employ tools of molecular modeling, atomistic simulations, and enhanced sampling to study how structural modifications in chromatin translate into differences in dynamics. These differences are often associated with distinct functions and purposes according to experimental input. This association sets a basis for our simulations to provide a molecular picture of the underlying mechanisms.
One example of an epigenetic modification is histone variant exchange as illustrated below. Centromeric nucleosomes are characterized by a unique histone variant called CENP-A (ice-blue) which replaces its canonical counterpart, histone H3 (dark blue). This alteration results in more flexible DNA termini in the centromeric nucleosome (bottom right) compared to the canonical nucleosome (bottom left). As it turns out, this flexibility is a physical feature necessary for the mitotic fidelity and proper segregation of chromosomes during cell division.
PhD Fellowship Position in Computational Biophysics Group
Izmir Biomedicine and Genome Center Computational Biophysics Group is seeking a motivated candidate to join their team as a PhD student to be funded by the TUBITAK 2232 program. Our group employs tools of high-performance computing, molecular modeling, and enhanced sampling to understand the biophysical processes that influence gene regulation at the molecular level.
The candidate should hold a Bachelor of Science or a Masters degree in sciences (Physics, Chemistry, Biochemistry, Molecular Biology, or Computer Science) or a related engineering field. You are expected to be able to communicate effectively in English and be familiar with or willing to learn scientific programming, molecular visualization as well as the biology and biochemistry of chromatin.
Interested candidates are encouraged to contact Dr. Seyit Kale (email@example.com) with a recent CV and their university transcript(s). For details on our research, please visit https://www.ibg.edu.tr/research-programs/groups/kale-lab/ .