Work done in the lab of Prof. Scott Pletcher, University of Michigan Medical School
Dr. Tuhin Subhra Chakraborty is a Research Specialist at the University of Michigan Department of Integrative and Molecular Physiology. He received a master’s degree in Zoology from Visva-Bharati University, Santiniketan, India, and a Ph.D. in Neurobiology from the National Center for Biological Sciences (NCBS), Bangalore, India. After completing a postdoctoral fellowship in System Neuroscience at the University of California, San Diego (UCSD), Dr. Chakraborty joined the University of Michigan, Ann Arbor, where he uses Drosophila melanogaster as a model organism to study the impacts of severe experiences on an organism’s survival and quality of life. In this pursuit, he is unraveling the links between perception and homeostatic control. Dr. Chakraborty published several research articles, reviews, and book chapters, and is a reviewer for several international journals.
How would you explain your research outcomes to the non-scientific community?
Sensory perception modulates aging, yet we know little about how. In this study, we (myself and my colleague Dr. Christi Gendron) focused on a neural population in the fruit fly brain that expresses serotonin receptor 5HT2A, the R2/R4 neurons. We found that these neurons act as a rheostat. Upon exposure to dead conspecifics, these neurons transduce sensory information in a way that modulates lifespan. Further, we discovered that Drosophila insulin-like peptides—Dilps 3 and 5, but not 2—were required to mediate lifespan effects due to death perception. Dilp regulation appeared after changes in R2/R4 neuron activity. Understanding the mechanisms by which neural circuits regulate aging could have implications for the development of targeted therapies in humans to slow down the aging process. The identification of specific neurons associated with aging provides valuable insights into how environmental conditions and experiences influence the rate of aging. The major significance of this work is that it provides insights into how a stressful experience, such as exposure to death, affects neural circuits and signaling systems in a way that may link to physical health and longevity.
“Our findings contribute to a better understanding of the aging process and of brain functions in the fruit fly. “
How do these findings contribute to your research area?
Aging is a complex process and can be affected both by the environment and genetics. Recent evidence, including our own findings, suggests that more complex sensory processes (e.g., detection of the opposite sex or dead conspecifics) influence a fly’s health and lifespan. In this study, we found that a handful of neurons in the fly brain are capable of influencing lifespan. Our work stimulates new questions about how distinct neural circuits impinge on well-known mechanisms of aging. Our findings contribute to a better understanding of the aging process and of brain functions in the fruit fly. The key factor in this process is the serotonin receptor 5-HT2A, located in these neurons. The identification of this evolutionarily conserved molecule provides valuable insights into how environmental conditions and experiences influence aging.
What was the exciting moment during your research?
In this study, we focused on identifying the neuronal populations in the fly brain that mediate perceptive events and their consequences. We examined neural activity in the fly brain following exposure to dead conspecifics. We were surprised to find that a small subset of neurons in the ellipsoid body of the central complex showed a significant increase in fluorescent intensity after death exposure relative to control flies. Further, when we silenced these neurons, we found that the survivorship of flies was unaffected by the presence of the dead. It was an exciting moment for us to discover that a handful of neurons can influence a fly’s lifespan.
What do you hope to do next?
Our study found that the activation of different ring neurons has different outcomes. This suggests that this neuropile may act as a rheostat to increase or decrease the rate of aging in response to sensory perception. Understanding the similarities and differences in the downstream functions of these neurons may provide insight into how this occurs. We also found that these neurons influence insulin-like peptide production and release. We want to determine how this limited set of neurons communicate with the median neuro-secretory cells of the adult fly brain.
Where do you seek scientific inspiration from?
My main motivator to pursue research as a career is my father, who was a Dean and Senior Professor in Agronomy at Visva Bharati University. I draw inspiration from my Ph.D. mentor, the late Prof. Obaid Siddiqi (National Center for Biological Sciences, Bangalore, India). My post-doctoral mentor, Prof. Scott Pletcher (University of Michigan, Ann Arbor), keeps motivating me to pursue innovation and out-of-the-box thinking in science. I also draw inspiration from my previous and current colleagues and friends both from the United States and India.
How do you intend to help Indian science improve?
My scientific journey started in India and I am very grateful for all the support I received as a master’s student at Visva Bharati University, and as a graduate student at National Center for Biological Sciences. India has immense potential for growth in the sciences. I hope to help improve international networking opportunities for Indian scientists. For scientific inquiry to find future success in India, we must engage industry with basic fundamental research and development.
Reference: Ring neurons in the Drosophila central complex act as a rheostat for sensory modulation of aging, Gendron CM*, Chakraborty TS*, Duran C, Dono T, Pletcher SD. Plos Biology 21 (6), e3002149
Edited by: Nikita Nimbark
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