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Staff profile

Overview

Dr Aakash Basu

Assistant Professor

Affiliations
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Assistant Professor in the Department of Biosciences

Biography

In 2013, Aakash Basu obtained a PhD in Applied Physics from Stanford University, USA, under the supervision of Prof. Zev Bryant. As part of his doctoral studies, Aakash developed single-molecule magnetic tweezers combined with Total Internal Reflection Dark-Field imaging to study how the topoisomerase DNA gyrase transduced chemical energy in ATP into mechanical work while supercoiling DNA. In October 2013, Aakash began a brief postdoctoral position at The Rockefeller University, New York, USA, working in the laboratory of Prof. A. James Hudspeth. He developed DNA-tethered magnetic tweezing-based assays, combined with sensitive voltage detection, to reveal the role of a cadherin protein filament in providing mechanical tension to gate mechanotransduction ion channels in inner ear hair cells. From 2015 – 2021, Aakash was a postdoctoral researcher in Taekjip Ha’s lab, initially at the University of Illinois, Urbana Champaign, USA (May 2015 – Dec 2015) and subsequently at Johns Hopkins University School of Medicine, USA (Jan 2016 – Dec 2021). Here Aakash developed novel tools that allow the application of genomic methods to study the structural biology of nucleic acids in high throughput. He broadly studied how the sequence-dependent mechanical properties of DNA are of functional importance in regulating protein-DNA interactions, and how pressure to preserve them has impacted the evolution of genomes. Since Dec 2021, Aakash was appointed as an Assistant Professor in Biochemistry at Durham University, as well as a Royal Society University Research Fellow. At Durham, Aakash continues to develop high-throughput assays to decipher the mechanical code of DNA and understand the scope of its functional relevance. Further, he complements high-throughput studies of protein:DNA interactions with single-molecule imaging methods.

 

Research Interests

·       Genomic methods development

·       DNA structure and mechanics

·       Protein:DNA interactions

·       Single-molecule biophysics

·       Biochemistry

We want to understand how biological information is stored in the complex physical and mechanical properties of DNA and RNA. Mechanical deformations of nucleic acids are ubiquitous in biology, and accompany almost all DNA:protein interactions. Such interactions, in turn, drive critical processes involved in the replication, transcription, repair, and packaging of genetic information. The intrinsic mechanical pliability of DNA to accommodate deformations might therefore play a significant role in regulating such critical processes. Some of the questions we are interested in are:

 

(1) What is the “mechanical code” of DNA? Specifically, how does local sequence impact the ability of DNA to locally bend, twist, and supercoil? 

(2) To what extent does evolution utilize the mechanical code to achieve control over critical DNA:protein interactions involved in the transcription? 

(3) How do chemical alterations to DNA, such as epigenetic modifications or chemical damage, modify the mechanical code? In turn, how do cells utilize dynamic control over DNA mechanics as a means of regulating DNA:protein interactions?

(4) How have physical forces impacted the evolution of genomes?

(5) How do DNA-manipulating molecular motors transduce energy efficiently, and how are they regulated by the structural and mechanical properties of the substrate DNA?

 

We develop novel sequencing-based methods to report on the sequence-dependent structure and mechanics of DNA in high-throughput. We employ machine learning and other mathematical tools to train predictive models for the sequence-dependence of DNA mechanics. Finally, we use single-molecule Fluorescence Resonance Energy Transfer (smFRET) and biochemical methods to decipher how DNA-binding motor proteins transduce energy and are regulated by the complex physical properties of substrate DNA.

Publications

Journal Article

Supervision students

Aditi Biswas

Research Postgraduate (PhD)

Bailey Forbes

Research Postgraduate (PhD)