Small molecule autophagy modulators research

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As part of the increasing academic and scientific engagements with India, Dr Sovan Sarkar (Birmingham Fellow) at the Institute of Cancer and Genomic Sciences in University of Birmingham (UoB) has recently collaborated with Dr Ravi Manjithaya at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bangalore on small molecule autophagy modulators. Their work, led by the JNCASR graduate student Mr Piyush Mishra, has been accepted for publication in the journal Autophagy (impact factor 9.108). Dr Carl Ward, postdoc in the Sarkar lab, assisted in this study. Autophagy is a cellular proteostasis pathway essential for human health. This vital biological process facilitates the clearance of unwanted macromolecules and damaged organelles from cells, thus maintaining cellular homeostasis and survival. Defects in autophagy lead to cell death and contribute to several diseases including cancer and neurodegeneration. Therefore, chemical modulators of autophagy have tremendous biomedical relevance. In this study, Mishra et al have conducted a high-throughput chemical screen in yeast to identify potent autophagy inhibitors that were shown to be effective in suppressing autophagic activity across three eukaryotic kingdoms: fungi, mammals and plants. These compounds have potential therapeutic applications for the treatment of cancer. This work was supported by Wellcome Trust/DBT India Alliance Intermediate Fellowship and JNCASR intramural funds to Dr Manjithaya, and Wellcome Trust Seed Award in Science and Birmingham Fellowship to Dr Sarkar, amongst others.

Dr Manjithaya and his research group have recently established novel high-throughput screening platforms in yeast pertaining to the drug discovery of autophagy modulators for therapeutic applications in diseases including cancer and neurodegenerative disorders. Previously, Dr Sarkar has identified a number of small molecule autophagy modulators that are of potential therapeutic relevance for diverse human diseases. The Sarkar lab, working on autophagy using human stem cells, aims to develop a pipeline originating from basic biology to drug discovery and potentially translate the findings for biomedical applications. This current collaboration between Dr Sarkar and Dr Manjithaya related to identifying novel modulators of autophagy strengthens the Birmingham–India partnership on biomedical science. 

This research has been submitted by:
Mishra P., Dauphinee A.N., Ward C., Sarkar S., Gunawardena A.H.L.A.N. and Manjithaya R. Discovery of pan autophagy inhibitors through a highthroughput screen highlights macroautophagy as an evolutionarily conserved process across three eukaryotic kingdoms. Autophagy (In Press)
[Note: The journal impact factor of Autophagy is 9.108]

The publication is currenly in production. The online version DOI is and is given ahead of time but will work only after the manuscript is okayed by the production editor.

UBII-Small molecule autophagy modulators research

(Top from left) Accumulation of autophagic vacuoles/vesicles in yeast, human cells and plants after treatment with an autophagy modulator identified in this study. Images courtesy of Piyush Mishra, JNCASR.
(Bottom from left) JNCASR senior author Dr Ravi Manjithaya and Birmingham Fellow Dr Sovan Sarkar.