Bryan Wilkins

The storage of genetic information within DNA sequences is the underlying code that defines an organism and it’s function. Genomic integrity is dependent upon the faithful replication and maintenance of DNA. Not only must the cell coordinate standard processes essential for gene transcription, DNA replication, and division, but it must also deliver rescue mechanisms in response to DNA damaging agents. 

Histone posttranslational modifications (PTMs) play an essential regulatory role in all aspects of chromatin function. Each of the core histones is vastly decorated with different PTMs, altering the side-chain chemistry and influencing changes in histone-DNA and histone-protein interactions. The chromatin landscape is shaped by an immense field of histone PTM writers, readers, and erasers. It is the concise balance of each of these factors that conserves chromatin plasticity and permits the fluid chromatin dynamics essential for proper function.

There remains an insufficient amount of data regarding the complicated molecular interactions that occur on the nucleosomal surface, particularly in the context of the living cell. My interests are focused on the subtleties of histone proteins and how their modifications influence chromatin architecture and molecular contacts that occur on the nucleosome. With the techniques we have established, we can now investigate the impact of histone PTMs in all aspects of chromatin biology as well as begin to illuminate the substantial interactome required for proper genome stability and integrity. 

To address chromatin function and structure in living cells we exploit a synthetic biology technique that allows for the expansion of the genetic code in Saccharomyces cerevisiae. This system requires an evolved tRNA/aminoacyl-tRNA synthetase pair that act as orthogonal cellular components to encode for unnatural amino acids in response to an amber stop codon. The recombinant expression of these orthogonal pieces allow for a wide assortment of non-native chemistries to be introduced at the genetic level.

In particular we are interested in the amino acid, p-benzoylphenylalanine. It contains a photo-inducible chemical crosslinking side chain that allows us to capture and monitor protein-protein interactions in vivo. We genetically encode this UAA into histone proteins and scan the nucleosomal surface for binding partners. We aim to expose nucleosomal protein-protein interactions and the mechanistic details of chromatin dynamics in yeast.

Neha Jain, Davide Tamborrini, Brian Evans, Shereen Chaudhry, Bryan J. Wilkins and Heinz Neumann. Interaction of RSC Chromatin Remodeling Complex with Nucleosomes Is Modulated by H3 K14 Acetylation and H2B SUMOylation In Vivo. iScience, 23, 101292. July 24, 2020.

https://www.sciencedirect.com/science/article/pii/S258900422030479X

Kyoko Hiragami-Hamada, Szabolcs Soeroes, Miroslav Nikolov, Bryan J. Wilkins, Sarah Kreuz, Carol Chen, Inti A. De La Rosa-Velázquez, Hans Michael Zenn, Nils Kost, Wiebke Pohl, Aleksandar Chernev, Dirk Schwarzer, Thomas Jenuwein, Matthew Lorincz, Bastian Zimmermann, Peter Jomo Walla, Heinz Neumann, Tuncay Baubec, Henning Urlaub, and Wolfgang Fischle. Dynamic and flexible bridging of H3K9me3 via HP1β-dimerization establishes a plastic state of condensed chromatin. Nature Communications, 7. 11310-11326. April 19, 2016.  

https://www.nature.com/articles/ncomms11310

Tom Kruitwagen, Annina Denoth-Lippuner, Bryan J. Wilkins, Heinz Neumann, and Yves Barral. Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation. eLife, 4. 332-351. November 28, 2015.

https://elifesciences.org/articles/10396

Bryan J. Wilkins, Nils A. Rall, Yogesh Ostwal, Tom Kruitwagen, Kyoko Hiragami-Hamada, Marco Winkler, Yves Barral, Wolfgang Fischle and Heinz Neumann. A cascade of histone modifications induces chromatin condensation in mitosis. Science, 343. 77-80. January 3, 2014.

https://science.sciencemag.org/content/343/6166/77

2015-present

Assistant Professor, Department of Chemistry and Biochemistry, Manhattan College

2010-2015  

Postdoctoral Fellow, University of Göttingen, Germany

2020

Faculty Fellow of the Catherine and Robert Fenton Endowed Chair in Biology

2019 

American Society for Biochemistry and Molecular Biology (ASBMB) outreach grant - The B³ Project - Biochemistry Bootcamp in the Bronx

2019

Manhattan College Summer Grant - Defining the genome-wide chromosomal occupancy of the RSC chromatin remodeler in yeast

2018-2020 

Michael J. and Aimee Rusinko Kakos Faculty Endowed Chair of Chemistry

2017-2021 

NIH AREA (Academic Research Enhancement Award) R15 1R15GM124600 - The spatiotemporal mapping of the RSC and SWI/SNF chromatin remodeler complexes on the nucleosome in living cells

2016 

Manhattan College Summer Grant - Exploring chromatin dynamics within the DNA damage response pathway in living cells

2011

Alexander von Humboldt Fellow - Spatiotemporal mapping of higher-ordered structures in vivo in Saccharomyces cerevisiae with the unnatural amino acid p-benzoylphenylalanine