Dr Abhinav Koyamangalath Vadakkepat

• 2024: Lecturer, MCB and LISCB

• (2017-2022) Postdoctoral Research Associate: ISMB, University College London and Birkbeck

• (2010-2017) Ph.D.: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. 

   > (2015-2017): Albert Einstein Centenary Fellow, Indian National Science Academy
   > (2012-2015): Council of Scientific and Industrial Research (CSIR, GoI) Senior Research Fellow
   > (2010-2012): Council of Scientific and Industrial Research (CSIR, GoI) Junior Research Fellow

• (2008-2010) M. Tech (Masters in Technology): West Bengal University of Technology, Kolkata, India. 

• (2004-2008) B. Tech (Bachelors in Technology): SCT College of Engineering, Kerala, India. 

Biography:

I studied Biochemical Engineering at University of Kerala, India and during my undergraduate research program got exposed to host-pathogen interactions, computational biology and structural biology working on the HIV protease inhibitor design. My fascination with infectious diseases and molecular microbiology continued during my postgraduate degree project where I studied mechanisms associated with pH stress tolerance and toxigenicity in Vibrio cholerae in close collaboration with National Institute of Cholera and Enteric Diseases, Kolkata, India. For my PhD, I  moved to the Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India to use X-ray crystallography to study structural biology of plant, mycobacterial and archaeal lectins. After successful completion of my doctoral degree, I joined Birkbeck, London in 2017 as a postdoctoral research associate at Birkbeck college and University College London to study Type IV secretion systems (T4SS) which are large macromolecular assemblies that power conjugation and are responsible for maintenance of genome plasticity and dissemination of antimicrobial resistance (AMR) in bacteria. These projects mainly involve extensive use of membrane protein biochemistry, single particle cryo-electron microscopy (cryo-EM), X-ray crystallography and biophysical chemistry.

Welcome to Abhinav (AKV) lab. We work on cell wall integrated nanomachines that underpin the biology of systems mediating genome plasticity, dissemination of antimicrobial resistance and bacteriophage resistance in bacteria. An outline of the key areas my group is interested in are given below. For a detailed description of the ongoing projects in my lab, please visit the Research Projects section our lab webpage at https://www.akv-lab.com/.

Our research is centered around two broad themes:

1. Conjugative systems in bacteria:
   
   Our lab is interested in understanding how bacteria use secretion systems for exchanging genetic material through conjugation to maintain genomic diversity and achieve saltational evolution into pathogenic species causing widespread infectious diseases related mortality. This exchange of genetic material between bacteria, also referred to as horizontal gene transfer (HGT) is fundamental to the dissemination of antimicrobial resistance (AMR) within bacteria, a formidable biomedical challenge, and an area of active research. After working extensively with gram- bacteria and studying Type-4 secretion systems (T4SS) involved in classical conjugation, our current focus is to understand how gram+ mycobacteria, a family of considerable importance in infectious diseases and AMR undertakes a distinctive form of HGT (called distributive conjugal transfer (DCT)) to facilitate its evolution into pathogenic mycobacteria and develop antimicrobial resistance. The overarching aim of this research program is to establish a structural basis for DCT by characterizing the multimegadalton membrane-integrated Type-7 secretion systems (T7SS) and associated complexes involved in substrate processing and translocation using a combination of biophysical chemistry and structural methods with a long-term vision of developing targeted antibiotics against these systems.



2. Bacteriophage defense mechanisms in bacteria:
   
   Research interest in bacterial-bacteriophage interactions has come to the centerstage due to its importance in bacterial evolution, as gene editing tools (CRISPR-Cas) and most importantly in the development of phage therapies to treat or prevent hard-to-treat bacterial infections and combat antibiotic resistance. Although this strategy has many advantages, the main drawback is the risk of encountering or favouring the emergence of phage resistant/insensitive bacterial pathogens, molecular mechanisms of which remain completely unexplored. In this arms-race between microorganisms, bacteria have evolved numerous defence strategies to combat phage infections like the Restriction-Modification Systems (RM), DNA degradation systems and CRISPR-Cas Systems. Our lab is particularly interested in characterizing the Abortive infection (Abi) system which is usually a measure of last resort as it involves the bacterial cell committing suicide after sensing infection before the phage can complete its replication cycle. Although a plethora of Abi systems are now known, we are particularly interested in dissecting how λ-lysogenic prophage encoded RexA/RexB Abi system prevents infection of other bacteriophages like the T4, T5 and T7 phages in E. coli. Research on Abi systems in bacteria is expected to accelerate the design of better bacteriophage-based therapies against persistent pathogens like M. tuberculosis, M. ulcerans, M. abscessus, C. difficile, P. aeruginosa, S. aureus, A. baumannii and K. pneumoniae.
   
   Strategy: Our goal is to understand how these biological processes work and to achieve this, we use a multi-disciplinary approach combining structural (X-ray crystallography and electron microscopy (cryo-EM)), molecular (cloning, tagging), membrane-protein biochemistry, biophysical (mass spectrometry, EPR, FRET, etc.), in-sillico (AL/ML-led molecular modelling and molecular dynamics) and cell biological (live-cell imaging and fluorescence microscopy) techniques.
   
   Environment: We collaborate extensively within the University of Leicester (UoL) ecosystem: Departments of Molecular Cell Biology (MCB), Respiratory Sciences (RS) and the Leicester Tuberculosis Research Group (LTRG) along-with inter-institutional collaboration with University College London (UCL) and University of Birmingham (UoB) for functional in-vivo characterization of conjugative secretion systems. We also collaborate with Department of Genetics and Genome Biology (GGB) and National Centre for Phage Research, UoL for our work on abortive-infection (Abi) systems. We access the resources available within the Midlands Cryo-EM Facility and Biophysics facility available within LISCB (Leicester Institute of Structural and Chemical Biology) for structural and biophysical characterization of protein-protein and protein-DNA complexes of interest.

Publications:

1. Jayaraman, V., Khan, S. A., Perinbam, K., Rakheja, I., Abhinav, K. V., Chaudhary, S., Pandey, A. K., Mitra, J. (2023). A comparative study of low pH tolerance and chitinase activity in  V. cholerae. (BioRxiv: https://www.biorxiv.org/content/10.1101/2023.02.13.528346v1).

2. Mallika, V., Abhinav, K. V., Bandyopadhyay, D., Mahendran, K. R., Sharaf, A., Pillai, M. R. and Soniya, E. V. (2023). Structural analysis unravels functional promiscuity of Quinolone 2 synthase-mediated Pks biosynthesis. (BioRxiv: https://doi.org/10.1101/2022.08.26.505429). 

3. Macé, K.*, Abhinav, K. V.*, Redzej, A., Lukoyanova, N., Oomen, C., Braun, N., Ukleja, M., Lu, F., Costa, T. R. D., Orlova, E. V., Baker, D., Cong, Q. and Waksman, G. (2022). Cryo-EM structure of a type IV secretion system. Nature, 607, 191-196. (*: equal contribution). 

4. Sivaji, N., Abhinav, K. V. and M. Vijayan. (2017). Crystallization and preliminary X-ray studies of a β-prism I lectin from Methanococcus voltae. Acta Cryst., Section F, 73, 300-304. 

5. Abhinav, K. V., Sharma, K., Surolia, A., Vijayan, M. (2016). Distortion of the ligand molecule as a strategy for modulating binding affinity. Further studies involving complexes of jacalin with β-substituted disaccharides. IUBMB Life, 69, 72-78. 

6. Abhinav, K. V., Sharma, K., Surolia, A., Vijayan, M. (2016). Effect of linkage on the location of reducing and non-reducing sugars bound to jacalin. IUBMB Life, 68, 971-979. 

7. Abhinav, K. V., Samuel, E., Vijayan, M. (2016). Archeal lectins. Identification through a genomic search. Proteins, 84, 21-30.  

8. Abhinav, K. V., Sharma, K., Surolia, A., Vijayan, M. (2015). Jacalin-carbohydrate interactions. Ligand distortion as a determinant of affinity.  Acta Cryst., D71, 324–331. 

9. Abhinav, K. V., Sharma, A., Vijayan, M. (2013). Identification of mycobacterial lectins from genomic data. Proteins, 81, 644-657. 

10. Chetnani, B., Kumar, P., Abhinav, K. V., Chibber, M., Surolia, A., Vijayan, M. (2011). Location and conformation of pantothenate and its derivatives in Mycobacterium tuberculosis pantothenate kinase: insights into enzyme action.  Acta Cryst., D67, 774–783. 

Reviews

1.   M. Vijayan and Abhinav, K. V. (2012). X-ray crystallography and Protein structure. Textbook of Biochemistry, Biotechnology, Allied and Molecular Medicine.

2.   Abhinav, K. V. and Vijayan, M. (2014). Structural diversity and ligand specificity of lectins. The Bangalore effort. Pure and Applied Chemistry, 86, 1335-1355.

ORCID: https://orcid.org/0000-0001-8202-7757

Google Scholar: https://scholar.google.com/citations?user=racGFNUAAAAJ&hl=en

• Conjugative secretion systems
• AMR in bacteria
• Mycobacterial host-pathogen interactions and evolution
• Phage-defence mechanisms in bacteria
• Phage biology and AMR
• Membrane protein biochemistry
• Biophysics
• Structural biology: X-ray crystallography and cryo-EM
   

ORCID

Google Scholar

Actively looking for PhD students. PhD projects are available in our lab, and we are also open for Masters projects and summer internships. Interested students should contact me directly.

1. University Gold Medal in B. Tech (Biochemical Engineering), University of Kerala (2008).
2. Best poster award in 18th International Biophysics Congress, Brisbane, Australia (2014).
3. Gold Medal for the Best PhD Thesis Award in Division of Biological Sciences, IISc Bangalore (2017).

• Conjugative secretion systems
• AMR in bacteria
• Mycobacterial host-pathogen interactions and evolution
• Phage-defence mechanisms in bacteria
• Phage biology and AMR
• Membrane protein biochemistry
• Biophysics
• Structural biology: X-ray crystallography and cryo-EM