Understanding the basic mechanisms of phagocytosis in the brain

Work done in the lab of Prof. Siddhesh S. Kamat at Department of Biology, IISER-Pune

About author

Shubham is a postdoctoral fellow (Bluefield Project to Cure FTD fellow) at Harvard Medical School and Harvard School of Public Health. He completed his doctoral training at the Department of Biology, IISER-Pune, where he had a fantastic opportunity to learn and work on various things ranging from chemical biology to neurobiology. He uses cutting-edge biochemical tools coupled with mass spectrometry and microscopy-based approaches to understanding the basic biology of aging, immunity and neurodegeneration.

Interview

How would you explain your research outcomes to the non-scientific community?

Renewal and replacement are the two most crucial elements for any thriving system with roaring excellence. For this, living machines (organisms) are engineered with an immense intrinsic ability to identify and clear ineffective, injured, or damaged parts and possibly replace them with new ones. This power is mainly vested in a specific type of cells in the brain – called microglia. They use enormously complex machinery to survey, identify and remove nonfunctional or damaged parts in the brain regions. In rare cases, failure of this machinery makes microglia go uncontrolled; they attack and remove even healthy parts of the brain without suitable replacements. This can compromise the function of the brain, visible in the form of mental disorders in humans. In our current study, we demonstrated that the enzyme ABHD12 has a crucial role in regulating the activity of microglia. Its inactivity can make microglia hyperactive in the brain, causing neurological disorders like PHARC Syndrome.

How do these findings contribute to your research area?

A few crucial questions in the field are: how microglia precisely identify and delete unwanted parts in the brain and when and why they turn toxic to cause brain diseases. The current report identifies ABHD12 as a new member of the complicated machinery that regulates the activity of microglia in the brain and explains why its inactivity causes PHARC Syndrome in humans. A detailed understanding of how all this is achieved still needs to be figured out.

“The current report identifies ABHD12 as a new member of the complicated machinery that regulates the activity of microglia in the brain and explains why its inactivity causes PHARC Syndrome in humans.”

What was the exciting moment during your research?

Seeing a robust phenotype (observations of abnormality) is one of the most exciting and best things in the life of most biomedical researchers. If you can reverse or rescue the phenotype, it’s a big plus and probably the first naïve sign that disease can be cured. It was exciting to see that the inactivity of just one enzyme (ABHD12) made these cells (microglia) go crazy and engulf more materials than they could probably digest.

What do you hope to do next?

Many things, I must say. But among many things, currently, as a postdoc at HMS, I am trying to understand why and how living organisms age, especially their nervous system? Approximately 3.5 billion years ago, the birth of the first life form also gave birth to the phenomenon of aging and subsequent death. Since then, this biochemical defect (aging) seems to be an essential factor in the prognosis of most diseases ranging from cardiovascular neurodegenerative to infectious diseases like COVID-19. Hopefully, someday we will learn to fix or alleviate this defect. No, not to be immortal but to fix the building problem of aging-associated diseases.

Where do you seek scientific inspiration from?

My scientific inspiration comes from several things. One of them is living organisms and their grand design. Suppose we calculate the raw material cost of living machines (mainly carbon); in that case, it’s a non-significant amount but what they can achieve after being assembled as a living entity is just awe-inspiring and magnificent. They are the most sustainable, renewable, self-propagating intelligent machines with the most innovative design ever thought. Though they still need to improve on their aging defects.

How do you intend to help Indian science improve?

Science serves best when learned and investigated at a global pedestal with extensive collaboration rather than unnecessary autophagic competition. COVID-19 can be an excellent case study for it.

With that said, I will be happy if I can make some contribution in the following three areas:

Capitalize on human scientific resources generated in India: Indian science (with limited resources) has been doing a remarkable job to generate highly skilled scientific human resources by picking, polishing and training world-class young scientists, thinkers and innovators along with making several progressive discoveries. I desire to find efficient ways to capitalize on this skilled human and scientific resource better. There seems to be a huge gap between talent nurturing and their utilization. Hopefully, any improvement in this can be of some use.
Expand aging research program: Indian age demography will shift from young to old (>60 years of age), and it will add to the massive burden on the already precarious and strained medical infrastructure. Building an aging research infrastructure that can find solutions to aging-associated diseases might be the best shot we have to succeed as a scientific and health welfare state.

Engage the non-scientific community in science: If publicly funded science aims to improve people’s lives in society, then we should possibly engage and explain them at our best. It would be mutually beneficial for both the scientific and nonscientific communities. Also, it might be an opportunity to bring science into the mainstream of society and politics. There are already excellent outreach programs by several institutions across India.

Reference

Shubham Singh, Siddhesh S. Kamat. The loss of enzymatic activity of the PHARC-associated lipase ABHD12 results in increased phagocytosis that causes neuroinflammation. EJN European Journal of Neuroscience, Volume 54, Issue 10 7442-7457.

Edited by: Vikramsingh Gujar

Meet the managers

Surabhi Sonam

Surabhi Sonam is an Assistant Professor. Along with teaching and research, she has a very strong interest in science communication. She has written several poems and blogs to communicate scientific principles and concepts. She is also volunteering with several science communication platforms as a content contributor and content editor. Under her supervision, her students have launched a scicomm magazine, Scinion which represents science in verbal and visual forms.

Sejal Dixit

Sejal Dixit is currently a 3rd-year student pursuing BSc triple majors in biotechnology, zoology, and chemistry from CHRIST (Deemed to be University). She loves to read, be it short stories, novels, magazines, or research articles. She is working with her college professor on a few papers, and wishes to pursue her master’s degree in stem cells and regenerative medicines. She has no problem socializing with new people and possesses leadership qualities. Her hobbies are dancing and traveling.

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