Honours and Fellowship:
Structural Biology – Macromolecular Crystallography
Chromatin Structural Biology
Histone proteins package eukaryotic DNA into chromatin. The dynamic DNA-protein complex called nucleosomes form the basic element of chromatin. All eukaryotic genomic processes, both natural and pathological, including transcription, replication, recombination, repair, chromosome segregation, carcinogenesis and viral infection can be fully understood only in the context of nucleosomes. The core of a nucleosome, called the nucleosome core particle (NCP) consists of fourteen turns of B-form DNA around an octamer of histone proteins, as can be seen in the image.
Nucleosome is known to be the binding platform for several protein factors. In order for a protein to gain access to chromosomal DNA/histone proteins, it needs to interact and/or compete with the histone proteins/DNA of the nucleosome. Studies involving nucleosomes are of greater significance as compared to isolated studies focusing on interaction of protein factors with individual histone(s) or DNA. So in addition to a couple of stand-alone chromatin structural biology projects, we are also looking at projects which combine the themes of chromatin biology and infectious diseases. In this regard, our group is interested in proteins from certain viruses for which nucleosome form a docking station. A combined biochemical, biophysical and crystallographic approach on complexes of host nucleosomes and interacting viral proteins is expected to reveal details of the interactions, thereby explaining several previously unknown mechanisms involved in the life cycle of the viruses. This understanding could probably be a step towards the identification of suitable drug candidates against those viruses that target viral replication.
Around the theme of chromatin structural biology, another of our interest is histone chaperones. Histone chaperones are a group of proteins that bind histones and regulate nucleosome assembly. Mode of action of several histone chaperones is not well-understood. Also, it is not completely clear regarding what decides the specificity of certain histone chaperones for H3-H4, H2A-H2B or histone variants. In order to better understand these molecular machines, we work on a few projects dealing with the structural characterization of some important, but poorly characterized histone chaperones.
Structural Biology of Clp Machinery Proteins
The caseinolytic protease (Clp) machinery is present in bacteria, plants and other eukaryotes. These proteases usually associate with Clp chaperone proteins which help in ATP-dependent unfolding of substrates which need to be taken in for proteolysis by the proteases. ClpD is a Clp-associated chaperone unique to plants. Plant ClpC and ClpD proteins both get localized into chloroplast stroma. However, our recent work has revealed that the structure of ClpD is quite different from ClpC in its N-terminus. Our interest on plant Clp machinery proteins is to understand their distinct roles in protein homeostasis and stress response. In addition, we also work on mycobacterial Clp chaperones due to their importance as a target in anti-mycobacterial research.
Infectious Disease Structural Biology
A couple of our chromatin structural biology and Clp machinery projects have infectious disease flavour. In addition, we also work on proteins involved in bacterial cell division, as well as proteins from infectious fungal and viral pathogens. More recently, we have started working on candidate proteins from the dreaded White Spot Syndrome Virus (WSSV) that infects cultured shrimps.
Over and above these, additional crystallographic projects are being taken up from time to time, on a collaborative basis.
Our in-house collaborators:
Other major collaborators:
As we have technical expertise in making nucleosome core particles and nucleosomal arrays, our group is open to collaborative projects dealing with nucleosome binding factors.
To know more about our group, please have a look at: www.dvasulab.com
[* Equal contributors] [# Co-corresponding authors]
Our Group Photo:
From left to right: Aritreyee, Annapurna, Ashish, Ajit, Nausad, Dileep, Ruchir, Manas, Ketul and Rajiv
|Funding agency||Title of the project||Duration|
|DBT||Bhubaneswar Biophysical Characterization Facility||4 years; from December 2019 (ongoing)|
|SERB||Unraveling the function of plant FKBP nucleoplasmins through structural studies||3 years; from December 2019 (ongoing)|
|DBT||Structural characterization of White Spot Syndrome Viral enzymes involved in viral nucleotide synthesis||3 years; from January 2018 (ongoing)|
|CSIR||Structural basis of dengue virus capsid protein interaction with the human death domain-associated protein DAXX||3 years; from October 2015 (completed)|
|SERB||Host nucleosomes forming a docking station for Dengue virus capsid protein C – a structural analysis||3 years; from October 2015 (completed)|
|DBT||Structural characterization of Influenza A virus matrix protein M1 interaction with host nucleosomes||3 years; from November 2014 (completed)|
dileepvasudevan [at] gmail [dot] com, dileep [at] ils [dot] res [dot] in
Nalco Square, Bhubaneswar-751023, India