Autophagy research collaboration on tuberculosis using human stem cells with International Centre for Genetic Engineering and Biotechnology in New Delhi

Under the UK-India Education and Research Initiative (UKIERI), Dr Sovan Sarkar (Birmingham Fellow) at the Institute of Cancer and Genomic Sciences in University of Birmingham (UoB) has been awarded the UKIERI DST Thematic Partnership Award with Dr Dhiraj Kumar at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi, India. 

The 3-year grant will be funded by the British Council to Dr Sarkar in UK and by the Government of India Department of Science and Technology (DST) to Dr Kumar in India. The project entitled “Investigating the regulation and manipulation of autophagy, mitophagy and xenophagy upon Mycobacterium tuberculosis infection in human embryonic stem cell-derived macrophages” will be undertaken jointly at UoB and ICGEB. Part of the research will be in collaboration with Dr Eva Frickel at the Francis Crick Institute in London, UK. Key research team members in the Sarkar and Kumar labs include the PhD students Ms Elena Seranova (UoB, UK) and Ms Surbhi Verma (ICGEB, India).

The UKIERI DST Award contributes to the increasing scientific engagements of UoB with India under the umbrella of the University of Birmingham India Institute. The Sarkar lab in UoB, primarily involved in the autophagy and human stem cell work in this project, aims to develop a pipeline originating from basic biology to drug discovery and potentially translate the findings for biomedical applications. The Kumar lab at ICGEB works towards understanding the host-pathogen interactions during Mycobacterium tuberculosis infection using high-throughput experimentation and integrative analytical approaches. The UK and the India research teams recently met in Bhubaneshwar in India during December 2017 at the India–EMBO Symposia on ‘Autophagy: Cellular mechanisms and significance in health and disease’. Dr Sarkar was a co-organiser of this conference where Dr Kumar was an invited speaker.

Tuberculosis is a devastating infectious disease caused by Mycobacterium tuberculosis (Mtb) resulting in 1.5 million annual deaths globally, thus posing a serious health concern in a number of low and middle income countries including India. Host innate defense mechanisms include removal of cellular Mtb through a biological process called autophagy, which is an intracellular degradation pathway for aggregation-prone proteins, damaged organelles like mitochondria (mitophagy) and pathogens (xenophagy). Autophagy is essential for maintaining cellular homeostasis and is thus vital for human health. This UKIERI DST funded research project will use cutting-edge technologies involving human stem cells and genome engineering, with the overall objective to understand the role of autophagy during Mtb infection in relevant human cellular platforms. The findings will be translated into novel therapeutic interventions for tuberculosis and related infectious diseases where autophagy acts as a protective pathway. The initial research work has been submitted for publication and has been uploaded at bioRxiv, a preprint server for biology.

Reference of paper: Sharma V., Makhdoomi M., Kumar P., Khan N., Singh S., Verma H.N., Luthra K., Sarkar S., Kumar D. Induction of autophagy by trehalose limits opportunistic mycobacterial infections in HIV-infected macrophages. bioRxiv (2017) doi: https://doi.org/10.1101/202697.

Photo legend:
(Top from left to right) Birmingham Fellow, Dr Sovan Sarkar; Francis Crick Institute Group Leader, Dr Eva Frickel; ICGEB Group Leader, Dr Dhiraj Kumar.
(Bottom from left to right) Sarkar lab PhD student at UoB, Ms. Elena Seranova; Microscopy image of cells expressing a fluorescent autophagy reporter; Kumar lab PhD student at ICGEB, Ms. Surbhi Verma.