In 2007, paleobiologist Erwin came to the conclusion that “there is nothing scientists enjoy more than the prospect of a good paradigm shift’’, referring to the concept of paradigm shifts by historian/philosopher of science Kuhn (1962). A similar paradigm shift was suggested when Waddington introduced the concept of epigenetic landscape to describe how gene regulation modulates development. In one of his many metaphors, Waddington illustrates a number of marbles rolling down the hill. The marbles inspect each groove on the slope and finally rest at the lowest points. These points indicate the eventual cell fates.metal ions.

Early studies done by Michael Meaney and Moshe Szyf provided evidence that the type and amount of nurturing a mother rat provides in the early weeks of rat’s infancy determine the rat’s stress response later in life. Pioneering work done by Meaney and Szyf opened an entire field of behavioural epigenetics. Depression is known to occur because of either genetic reasons or epigenetic factors. It can be triggered due to family history, lifestyle changes, medicines, health issues, trauma, substance abuse etc.

Summer of 2019 found me in Centre for Cellular and Molecular Biology (CCMB), Hyderabad straight into the Epigenetics and Neuropsychiatric Disorders Laboratory under the able guidance of Dr Arvind Kumar. The lab mostly focuses on Major Depressive Disorder (MDD). The cause of depression and the molecular basis of treatments are still poorly understood. However, recent findings suggest that epigenetic modifications and mechanisms might be biological markers of depression and antidepressants’ efficacy or it may be directly involved in the pathophysiology of depression and action of antidepressants

What exactly is epigenetics? The word “epigenetic” literally translates to “in addition to changes in genetic sequence.” This includes any process that alters gene activity without changing the DNA sequence and leads to modifications that can be transmitted to daughter cells (although experiments show that some epigenetic changes can be reversed). One of the best understood epigenetic processes is DNA methylation. Another significant epigenetic process is chromatin modification. These modifications alter chromatin structure and thus can influence gene expression. In general, tightly folded chromatin tends to be shut down, or repressed, while more open chromatin is functional or expressed.

Behavioural disorders appear unlikely to occur due to single gene mutation as behaviour is a polygenic trait. However, it is likely that chromatin remodelling or epigenetic mechanisms might induce repression or silencing on the regulatory regions of many genes including the chromatin regulators or remodelers in particular circuitry of the brain, causing depression and related affective disorders.

My work in Arvind Sir’s lab involved understanding the effect of a novel demethylase enzyme on pan histones (a family of proteins that associate with DNA in the nucleus). The demethylase was overexpressed (transiently) in HEK293T cells (human embryonic kidney cell line), followed by protein isolation, quantification and lots of western blotting. In addition, I was also helping with behavioural assays. CCMB’s summer program involved lecture sessions, every Tuesday, introducing us to different fields of research. The lab had an excellent work culture and the people were really approachable. We would have latenight discussion ranging from experiment development to black holes. Last but not least, sitting on the banks of the Musi River, the city of Hyderabad gave me a lot to cherish.