Anmol Adhav – University of Copenhagen

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Anmol Adhav

Name: Anmol Adhav
Twitter: anmolsadhav
Email: aadhav@ibv.csic.es

Affiliation:

Instituto de Biomedicina de Valencia- CSIC
Calle Jaime Roig 11,
46010 Valencia

Education and Experience:

After completing my higher secondary education in 2011 and aiming to pursue a career in Biological sciences I joined a unique postgraduate program in Biotechnology, 5 Years Integrated Master of Science, at the Institute of Bioinformatics and Biotechnology (iBB), University of Pune, Pune, India.

During my 5 years at the iBB, I learnt various fields of Biotechnology including Molecular biology, Microbiology, Bioinformatics, Plant Biotechnology, Immunology and Biochemistry.  I also got an opportunity in my 3rd Year to work on an in house project with Dr. Vaijayanti Tamhane (Assistant Professor, iBB, Pune) which introduced me to the research environment and laboratory techniques in molecular biology and biochemistry.  

In December 2015 I joined National Chemical Laboratory (NCL), Pune for my dissertation project  with Dr. Rakesh Joshi (Assistant professor, iBB, Pune) and Dr. Ashok Giri (Senior Scientist, NCL, Pune) on the topic “Heterologous Expression, Biochemical Characterization and Crystallization of Trehalase from Plutella xylostella gut symbiont Enterobacter cloacae.” During the tenure of this project, we collaborated with Dr. Gayathri Pananghat (Assistant Professor, Indian Institute of Science Education and Research (IISER), Pune), who is an expert in X-ray crystallography. This project helped me to gain hands on experience in heterologous protein expression, purification, biochemical characterization and crystallization of proteins. I completed this project in May 2016.

At iBB I got a chance to do one year Master of Technology (M.Tech Research) from August 2016 to August 2017. We decided to use the data obtained from previous work to explore trehalases as a specific target for devising new insect control strategies.  During this one year, I did studies with the inhibitor molecules by testing them in vitro and in vivo.  The excellent results coming from all the work that I did fetched us some publications.

ESR2: Structural and functional characterization of histidine kinase-inhibitor complexes

My Project

Two-component systems (TCSs) are the most abundant signalling devices in bacteria involving two proteins, a sensor histidine kinase (HK) and a effector response regulator (RR). Signalling by these systems start by the HK autophosphorylation that in a second step transfer this phosphoryl group to the cognate RR, which regulate (mainly) the gene expression. HK autophosphorylation is mediated via the catalytic and ATP-binding (CA) domain, which binds to ATP and phosphorylates the HK at a conserved histidine residue in the dimerization and histidine phosphotransfer (DHp) domain. The CA and DHp domains are conserved and present in all HKs, whereas the remaining sensor and modulator domains are variable. TCS are prevalent in bacteria, play key roles in virulence and antibiotics resistance and in several cases are essential, but are absent in mammals. Thus, these systems are perfect target for the design of inhibitors with antibiotics activity.

In our laboratory, we have started a structure-based drug design project taking as a target the CA domain of the histidine kinase CheA from Thermotoga maritima and using X-ray crystallography as a technical approach. The main objective of this work will be to provide the collaborators with the structural and biochemical information about the drug-histidine kinase complexes. Crystal structures of CA domain-small molecules complexes will be used as templates for in silico design/modification of a second generation of compounds (ESR 1). These new compounds will be synthetized (ESR 3) and will be used for in vitro activity and affinity analysis over a range of HKs coming from different bacteria by means of Biochemical and Biophysical approaches. This will also be followed by antibacterial activity testing (ESR 4).