Projects - Ph.D students (Joining January 2027)

Recommended Reading: Special Issue: Cell Biology of the Nucleus, Journal of Cell Science

Contact: kunsen@iiserpune.ac.in, kundansengupta@gmail.com, Cell: 7709582989 to schedule a meeting.

Project#1: How the "Feel" of cells in our Body impacts Cancer?

Imagine trying to grow a plant. It will grow very differently on a hard, flat rock than it will in soft, rich soil. Cancer cells are similar: they behave differently depending on the "feel" of their surroundings. This project is part of a new field that mixes biology, physics, and engineering. It explores a simple but important idea: our bodies are soft, but for decades, scientists have studied cancer cells by growing them on extremely hard surfaces like plastic or glass lab dishes. We're asking: What if the hardness of the plastic dish is giving us the wrong idea about how cancer works? A team of CBL students (Jayati Khanna, Anjitha Nair, Malhar Chitnis, Jashan Kler, and Rohith Ragesh) made an exciting discovery. They grew cancer cells on special soft gels that have similar stiffness as real human tissues. They found that when cancer cells are on these soft, body-like surfaces, they react to chemotherapy drugs in a completely new and unexpected way. Specifically, when the chemo damages the cancer cell's DNA (which is how most chemo works), the cells on the soft gel try to repair themselves differently than cells on hard plastic. The Big Questions We're Answering: This discovery leads us to two key questions: 1. What exactly are these cancer cells doing on soft surfaces that we've never seen before? 2. How can we stop it? Can we use this new knowledge to create better drugs that kill cancer more effectively, especially in the very early stages before it spreads? How We're Doing It: To answer this, we use a mix of lab techniques. We create special soft gels (called hydrogels) to grow the cells on, then use powerful microscopes and imaging to watch how they behave. We also use other tests to study the chemistry and biology of what's happening inside the cells. Essentially, we're trying to understand cancer in an environment that's more like the human body, hoping it will reveal new ways to fight it.

Project#2: Nuclear envelope and its crosstalk with chromatin modifiers in cancer cells: A truly novel and intriguing question in cell biology is: how does the Nuclear Envelope (NE) function as a sensor of external mechanical forces ? How does this impinge on signalling pathways in cancer cells? Does this impact expression of oncogenes and tumor suppressor genes? We are studying the biology of nuclear envelope proteins in cancer cells and especially when cancer cells are cultured on softer substrates. We have previously shown that the expression of nuclear envelope proteins is selectively altered on softer substrates. Furthermore, we found distinctive changes in the levels and localization of active and inactive histone marks that regulate gene expression. However, the mechanisms by which NE proteins crosstalk with histone modifiers, especially in the context of substrate stiffness and how these effects impact cancer initiation and progression are largely unanswered. CBL PhD Student - Jayati Khanna has pioneered and initiated novel experiments in the emerging subject of nuclear envelope biology and mechanical signals in cancer cells. 

Project#3: Role of nuclear architecture in Epithelial to Mesenchymal Transitions (EMT) in cancer cells: The nucleus is a central regulator of almost all fundamental processes in cells. However, how nuclear envelope proteins regulate mechanisms of initiation and progression of cancer cells, for instance during EMT is an intriguing question. In a project initiated and pioneered by former CBL PhD student - Dr. A K Balaji, we have found a novel role of nuclear lamins in regulating EMT in breast cancer cells. However, the mechanistic basis of how lamins and Linker to Nuclear Cytoskeletal Complex (LINC) proteins orchestrate and regulate EMT initiation and progression is an uncharted territory. Furthermore, how these processes impact genome and chromatin dynamics is a key intriguing question in the field. especially in the context of cancer cells. 

Project#4: Functional characterization of Nucleolar-Nuclear crosstalk in Epithelial Mesenchymal Transitions in cancer cells: In another recent study, former CBL-PhD student Dr. Santam Saha, has pioneered a novel area of research to address the role of the nucleolar protein Fibrillarin (Fbl) in regulating nuclear architecture and function. In addition to its enzymatic function as a 2'O-Methyltransferase which modifies rRNA, Fbl also regulates nuclear and cellular architecture since the depletion of Fbl enhances cell migration rates and EMT in cancer cells. The mechanistic underpinnings of such a process are finely intertwined with intriguing aspects of cellular architecture and physiology, which we aim to unravel in the context of cancers. 

Project#5: Role of nuclear lamins in DNA damage Repair and Cell migration: While the majority of studies have focused on static systems of understanding DNA damage response and repair (DDR), the mechanisms by which DDR is regulated in migrating cancer cells remains a mystery. Here, we induced DNA damage in migrating cancer lung cancer cells. CBL PhD student - Anjitha Nair has pioneered to address how cells mitigate DDR during cell migration. The molecular mechanisms of how DDR is initiated and its contribution to cell migration in cancer cells, is a relatively uncharted field in cancer biology. 

Project#6: Role of Nucleoporins in genome instability: Nucleoporins are channels that regulate the import and export of RNA and macromolecules into and out of the nucleus. Previously, former CBL PhD student - Dr. Ajay Labade performed pioneering studies to show that Nucleoporin 93 (Nup93) represses the HOXA gene cluster in cancer cells. Interestingly, Nup93 and the chromatin organizer - CTCF occupy mutually exclusive regions of the HOXA gene cluster thereby orchestrating the timely organization and expression of HOXA genes upon induction of differentiation. CBL PhD student - Neeta Parmar is now initiating an exciting project to address the role of Nups in the regulation of chromosomal and genome stability in cancer cells. 

Project#7: Functional characterization of Lamin-telomere crosstalk to protect cancer cells from chromosomal losses:  Former CBL PhD student - Dr. Shalaka Patil (Faculty, MIT World Peace University) pioneered this research to demonstrate that the Lamin B Receptor (LBR) is required for the maintenance of normal chromosome numbers. LBR loss not only induces loss of chromosomes, but also alteres the 3D spatial locations of chromosome territories in the interphase nucleus. She also showed that an intricate molecular feedback between lamins and nuclear envelope protein Emerin, plays a crucial role in the maintenance of genome and chromatin organization. Furthermore, the depletion of the Lamin B Receptor (LBR) showed specific chromosomal losses, with the concomitant signalling and upregulation of telomere proteins (TRF1, TRF2). Here we aim to uncover the lamin-telomere centric mechanisms that regulate chromosomal stability in cancer cells.  CBL PhD Student - Yamini Mosamkar is initiating studies centered on studying LBR. Intriguing experiments involve studying 1. LBR depletion on nuclear envelope proteins - using fixed and live cell imaging approaches will be used to quantify the effect of LBR depletion on nuclear envelope proteins. 2. Monitoring the effect of lamin, LBR depletion on telomeres - we will monitor the effect of depleting lamins on telomere length using Telo-FISH. 3. Functional association between lamin and telomere proteins - we will study the effect of modulating lamin levels on telomere proteins via biochemical, imaging and omics based approaches.