First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Mohima Mukherjee is first author on ‘Endoplasmic reticulum stress impedes regulated secretion by governing key exocytotic and granulogenic molecular switches’, published in JCS. Mohima is a PhD student in the lab of Dr Bhavani Shankar Sahu at the National Brain Research Centre, Manesar, India, investigating the molecular mechanisms of regulated secretion involving dense core vesicles and synaptic vesicles in neurons and neuroendocrine cells.

Mohima Mukherjee

How would you explain the main findings of your paper in lay terms?

Think of neurons and neuroendocrine cells as miniature factories that manufacture and dispatch cargo packaged in dense core vesicles and synaptic vesicles. Like any factory that has its own control centre, these cells have the endoplasmic reticulum (ER). A stressed ER interferes with the production and delivery of dense core vesicles and synaptic vesicles, leading to health complications. We observed that ER stress significantly hinders the timely delivery of these packages, like a factory experiencing delays in product shipments. Remarkably, reducing ER stress alleviates this delay. Further investigation revealed that ER stress causes a reduction in levels of SNAP25, a key protein responsible for package delivery, and that this reduction is the result of activation of another protein, ATF4. Our study demonstrates that ER stress disrupts the delivery of vital messages, potentially contributing to health problems. Understanding this process could pave the way for developing treatments for related diseases.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Working with neuroendocrine cells posed significant challenges due to their notorious resistance to transfection. Complicating matters further, inducing ER stress augmented this issue, making dual transfection particularly daunting. However, we remained persistent in optimizing transfection and treatment protocols. We established standardized procedures that significantly improved transfection efficiency in PC12 cells. This facilitated our imaging and overexpression experiments and enabled more robust and reliable results in our research.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

The moment when we found that ATF4 (also known as CREB2), which is the downstream target of the PERK–eIF2α arm of ER stress, could negatively modulate the expression of SNAP25. We conducted multiple experiments to substantiate this observation. When we discovered that inhibiting ATF4 restored SNAP25 levels and enabled the cell to respond to stimulation, my PI and colleagues burst into joy and were spellbound by the neat correlations among various experiments.

Why did you choose Journal of Cell Science for your paper?

Having my research published in the renowned Journal of Cell Science is a source of great joy and pride. As well as its longstanding reputation and history of landmark discoveries in cell biology, the rigorous peer review process at JCS underscores its status as a top publication in the scientific community. I am thrilled that my work aligns with the themes and standards of JCS, marking a significant achievement in my scientific journey.

Dense core vesicle exocytosis indicated by a fluorescence burst of NPY–pHTomato upon 100 mM KCl stimulation in PC12 cells, which is absent in cells experiencing ER stress.

Dense core vesicle exocytosis indicated by a fluorescence burst of NPY–pHTomato upon 100 mM KCl stimulation in PC12 cells, which is absent in cells experiencing ER stress.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

I have been incredibly fortunate to have a supportive network of individuals who have shaped my research journey. Dr Bhavani Shankar Sahu, my PhD advisor, has been a guiding light and has provided invaluable mentorship. He strongly believed in me and my abilities. Chandramouli Mukherjee, a senior colleague, has been instrumental in co-formulating hypotheses and designing experiments. Both helped and empowered me to become a rigorous scientist, and they have been patient with my errors. My co-authors had a tremendous role in executing specific tasks and enabling me to consolidate my research question. Lastly, my heartfelt gratitude goes to my mother, Koyeli Mukherjee, whose unwavering belief in me has been the cornerstone of my success in science.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

From my earliest memories, ‘why’ has been my favourite word, igniting a curiosity that has shaped my journey. With the unwavering support of loved ones, I have delved into the wonders of science, particularly the life sciences, fulfilling my desire to explore and allowing me to contribute meaningfully to society. I am deeply grateful for the privilege of pursuing knowledge and discovery, guided by a passion that continues to drive me forward.

Who are your role models in science? Why?

Born a year after Kalpana Chawla's inspiring mission as a scientist on STS-87, I grew up aspiring to emulate her courage and determination. Kadambini Ganguly, India's pioneering female doctor, fuelled my passion for life sciences with her incredible achievements. The 2020 Nobel laureates Jennifer Doudna and Emmanuelle Charpentier epitomize scientific excellence, motivating me to push my boundaries in the pursuit of knowledge and innovation.

What's next for you?

Currently, I am focusing on a few other projects and finishing my PhD, after which I would like to continue my career in academic research.

Tell us something interesting about yourself that wouldn't be on your CV

Trained in Hindustani classical music, I find solace and inspiration in exploring the intricate melodies of various ‘raagas’. Alongside my musical pursuits, I am drawn to the narratives of mythological tales, indulging myself in the depths of ancient wisdom. Beyond my artistic passions, my heart resonates deeply with the plight of stray animals. In the future, I aspire to dedicate myself to initiatives that uplift and protect these beloved creatures. During my bachelor's studies, I tried to make a positive impact by visiting orphanages, where I engaged children in conversations about the spread and remedies of viral diseases, empowering them with the knowledge to safeguard their health. Witnessing their smiles and empowerment filled my heart with joy, reaffirming my commitment to serving underprivileged communities and spreading happiness wherever I go.

Mohima Mukherjee's contact details: National Brain Research Centre, NH-8, Manesar, Gurgaon, Haryana 122052, India.

E-mail: [email protected]

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Endoplasmic reticulum stress impedes regulated secretion by governing key exocytotic and granulogenic molecular switches
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J. Cell Sci.
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