ESR6 – Chethan Kumar Krishna, Ruhr-University, Bochum, Germany

Chethan.Krishna@ruhr-uni-bochum.de

Systems biochemistryInstitute of Biochemistry and Pathobiochemistry

Ruhr-University Bochum, Bochum, Germany

Supervisor: Prof. Dr. Ralf Erdmann

I obtained master’s degree in Biochemistry from University of Mysore, India. During my Post-graduation, I have worked on two dissertation topics entitled “Probing Small Molecule as Modulator of Apoptosis in Lung Carcinoma” and “Local and systemic toxicities induced by Echis carinatus venom: Neutralization by Unconjugated bilirubin and its derivative”.

Subsequently, I worked as a Research Associate in Immuno oncology team, Discovery Biology unit at Syngene international limited, Bangalore, India. I was mainly involved in studying Immune cells and their effector function in the presence of bispecific antibody targeted against specific tumor cell lines.  I was also involved in the development and validation of various biochemical and cellular assays for screening of the bi-specific antibodies targeted against tumor antigens (TAA).  I was part of the integrated drug discovery programs where I screened small molecule inhibitors that target various kinases through various cell-free and cell-based assays.

Project title: Identification of novel glycosomal membrane proteins including glycosomal metabolite transporters

Insect-transmitted infections of trypanosomatid parasites lead to trypanosomiasis and leishmaniasis in humans. These neglected tropical diseases pose a major concern for human health as well as livestock. Therapies against these infections are ineffective, have severe side effects and drug-resistant strains are emerging. Therefore, there is an urgent need for development of new drugs.

Trypanosomes possess a unique peroxisome-related organelle called glycosome. Glycosomes compartmentalize glycolytic enzymes and other essential metabolic pathways. Glycosomes are essential for the survival of the parasites, therefore are considered as an attractive drug target. Like peroxisomes, glycosomal proteins are imported post-translationally into the organelle. Peroxins (PEX) mediate peroxisomal/glycosomal matrix and membrane protein import.

PEX19 is the cytosolic receptor for the newly synthesized peroxisomal membrane proteins (PMPs) in the cytosol. PMP proteins contain a membrane peroxisome targeting signal (mPTS), which is recognized and bound by PEX19. The PEX19-PMP complex docks at the peroxisomal membrane by binding to PEX3 and PEX16. PMP cargoes are inserted into the membrane and PEX19 is released for another round of protein import. The mechanism of cargo insertion and receptor release is still poorly known.

In this project, PEX19 complexes or glycosomal membrane proteins will be isolated and characterized. Additionally, bioinformatic analysis will be performed to identify homologs of known or novel PMPs.

Two major expected accomplishments of the study are:

1) identification of novel glycosomal membrane proteins, including glycosomal metabolite transporters.

2) Establishment of a screen to identify inhibitors of PEX19-PMP binding, as a strategy to disrupt glycosomal membrane protein targeting.

Gaining insights into pathogen cell biology metabolism and aspiration in scientific research and innovation towards novel therapeutic interventions.

In my spare time, I take online classes to improve my writing skills. And I like to travel, which gives a new experience and a great opportunity to know about different cultures.I am an avid photographer. I picked up this hobby only a couple of years ago, so it’s relatively fresh.  I started uploading some of these photographs on Instagram and people seemed to really like them. This encouraged me to spend more time on gaining basic photography skills like framing and light. Photography has enriched me with having a broader perspective and made me a keen observerCuriosity is the motivational force to understand how and why things happen the way they do. I personally believe that everything follows a pattern, the desire to understand this pattern and that of everything around us drives us towards science which provides us the path.

 

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grant number 812968