Prospective Students

Interview results will be announced on the following link https://dbg.iisc.ac.in/phd-interviews-2025/

The following faculty are planning to take Ph.D. students in this term (2025 cycle).

1. Dr Maya Raghunandan
2. Dr Sona Rajakumari
3. Prof Srimonta Gayen jointly with Prof Deepak Kumar Saini
4. Prof Tanweer Hussain
5. Prof Deepak Kumar Saini jointly with Prof Ramray Bhat
6. Prof. Annapoorni Rangarajan
7. Prof. Annapoorni Rangarajan jointly with Prof Srimonta Gayen

PI: Maya Raghunandan

Telomere Integrity and Molecular Oncology Research Laboratory

Background: The key objective of our lab is to identify, understand and exploit therapeutic vulnerabilities in biomarker-defined subsets of cancers, with emphasis on highly aggressive childhood cancers.

About 10% of all cancers are characterized by dependency on a unique biological phenomenon for achieving cellular immortality: Alternative Lengthening of Telomeres (ALT⁺) accompanied with highly unstable genomes. These cancers are particularly enriched in aggressive solid tumours in children, a population where targeted therapeutic approaches are currently limited.

Project details: The primary objective of this project is to identify & functionally characterise novel therapeutic targets for ALT⁺ cancers.

Our focus will be to identify proteins that either directly affect the telomere maintenance pathways or whose up/down regulation alters existing molecular pathways that create new targetable vulnerabilities in ALT⁺ cancers. We will discover the role of thus identified target within the complex molecular DNA damage response pathway protein network driving ALT-biology, dissect the underlying molecular details and validate the new therapeutic vulnerability in ALT⁺ cancers.

The incoming PhD student will be trained to lead a multidisciplinary project involving in silico metadata analyses, high-throughput genetic engineering (CRISPR-based) screens, and functional biology experiments using biochemistry and advanced microscopy-based approaches in human patient-derived cancer cell models. As the project lead, the student will also be involved in establishing new patient-derived cellular models in upcoming collaborations with clinical oncologists and potentially conduct clinical genomics analyses.

Please visit our website to learn more about me and our lab’s upcoming research.

https://sites.google.com/view/mayaraghunandanphd/research-vision

PI: Sona Rajakumari

The research program in our laboratory focuses on key transcription factors and RNA-binding proteins that regulate liver and adipose tissue function, and maintenance of pre-adipose stem cells under various metabolic conditions, including diet-induced obesity, aging, type 2 diabetes, etc. We employ several cutting-edge approaches to address our research hypothesis, including transcriptomics, lipidomics, and conditional or tissue-specific knockout and/or transgenic mouse models.

Project 1: Deciphering the epigenetic role of TET1 and TET3 in liver function

Our laboratory has generated liver-specific Tet1 knockout mice and will be employed to address lipid and mitochondrial homeostasis in the liver. Also, explore the TET1 and TET3 functions in detail during aging and fatty liver disease (Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Project 2: Transcriptional and post-transcriptional function of MATR3

MATR3 is an RNA-binding protein known for its role in transcription, RNA processing, mRNA stability, and splicing. The key question in this project is: Does MATR3 regulate post-transcriptional or splicing events during adipocyte lineage commitment and development? We employ biochemical, molecular, and in vivo murine models to study the physiological function(s).

 References:

1. Jain R, Rajendran R, Rajakumari S* (2025) Diet-induced obesity dampens the temporal oscillation of hepatic mitochondrial lipids. Journal of Lipid Research 1:100790.
2. Rajendran R, Suman S, Divakaran SJ, Swatikrishna S, Tripathi P, Jain R, Sagar K, Rajakumari S* (2024) Sesaminol alters phospholipid metabolism and alleviates obesity-induced NAFLD. FASEB J. 38(14): e23835.
3. Divakaran SJ, Srivastava S, Jahagirdar A, Rajendran R, Sukhdeo SV, Rajakumari S*. (2020) Sesaminol induces brown and beige adipocyte formation through suppression of myogenic program. FASEB J. 34(5):6854-6870.
4. Rajakumari S, Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, Reed RR, and Seale P. (2013) EBF2 Determines and Maintains Brown Adipocyte Identity. Cell Metab. 17(4):562-574.

PI: Srimonta Gayen jointly with Deepak Kumar Saini

Exploring the link between epigenome and metabolome in ageing among the Indian population

Epigenetic regulation plays an important role in controlling gene expression during development. Emerging studies indicate that as we age, cells undergo aberrant epigenetic changes that can affect health and longevity.  This project investigates ageing through the lens of epigenomic state among Indians, offering graduate students a unique opportunity to pioneer epigenome-based ageing research in an understudied demographic. By combining advanced next-generation epigenomics and bioinformatics, the project aims to uncover population-specific biomarkers and build India’s own epigenetic ageing clock based on DNA methylation patterns. In addition, the study will examine how age-related epigenetic changes are linked to age-associated metabolic alterations, providing deeper insights into the biological mechanisms of ageing.

PI: Tanweer Hussain

The synthesis of proteins using genetic information and its regulation is a fundamental process in all life forms. These processes play an important role in many key life processes including early embryonic development, learning and memory as well as in response to cellular stress. Although translation initiation is a fundamental and indispensable process, many of its aspects are poorly understood.  We employ biochemical, mutational and structural biology approaches to understand the molecular details of the initial steps of protein synthesis and to figure out how it is regulated. This is essential for developing novel therapeutic strategies for many human disorders/ cancers and against bacterial, fungal and viral infection.

We have made good progress in understanding eukaryotic translation initiation and its regulation (see recent publications). The incoming PhD student would build up on the ongoing project to understand the molecular details of eukaryotic ribosomal pre-initiation complexes in yeast and plants, using molecular biology, biochemistry, and structural biology techniques.

For further details of the project, contact Prof. Tanweer Hussain (Lab: GB-04; Email: hussain@iisc.ac.in)

PI: Deepak Kumar Saini jointly with Ramray Bhat

Discovering new drugs to combat ovarian cancer

Ovarian cancer is the third most common cancer in women in India and worldwide. It is characterized by rapid metastasis, long periods of spread before diagnosis, and resistance to chemotherapy. Several patients who respond to conventional chemo drugs develop refractoriness to the same afterwards. This necessitates discovery of new drugs, which can be tested in sophisticated in vitro and ex vivo models of ovarian cancer.

The project will involve: Time lapse, confocal, electron microscopy, Systems biology, Pharmacological screens, in vivo drug testing, Cell and molecular biological assays, Organoid and 3D culture, Multiscale modeling, Bioinformatics, and multiomic approaches.

For more details, please refer to- https://sites.google.com/site/sainislab/ and https://morphogenesisiisc.wixsite.com/home

PI: Annapoorni Rangarajan

Cancer and Stem Cell Biology lab

Impact of Diabetes and Aging in Mammary Gland Stem Cell Biology and Breast Cancer:

Adult stem cells of the mammary gland are critical for not only the development of the mammary gland during puberty, but also for its expansion during cycles of pregnancy and lactation. Given the extensive proliferation of mammary gland stem cells during these developmental processes, they remain prime targets for breast cancer initiation. Thus, it is important to understand the mechanisms that regulate the normal mammary gland stem cells.

Diabetes and aging are associated with increased breast cancer risk and progression. Diabetes-associated hyperglycemia and metabolic perturbation can alter mammary stem cell proliferation and cell-fate. Age-related accumulation of senescent stromal cells, and changes in epigenetic markers which control gene expression, can also affect mammary stem cells and their behavior. Thus, both diabetes and aging can affect stem cell function, quantity, and fate, potentially leading to an increase in the population of stem cells that are less functional or more prone to transformation.

This project will aim to understand the impact of diabetes and aging on breast tissue architecture, stem cell regulation, stromal cell interaction, breast cancer initiation and progression. The study will employ cell culture, 3D organoid models, fresh and archived patient samples, microscopy, flowcytometry, molecular biology and omics strategies. The project also aims to test the beneficial effects of nutraceuticals and other interventions to mitigate the adverse effects.

References-

• Dey D, Saxena M, Paranjape AN, Krishnan V, Giraddi R, Vijaya Kumar M, Mukherjee G, and Rangarajan A. (2009). Phenotypic and Functional Characterization of Human Mammary Stem/progenitor Cells in Long Term Culture PLoS ONE, 4(4):e5329.
• Balachander GM, Balaji SA, Rangarajan A ^*, Chatterjee K ^*. (2015). Enhanced Metastatic Potential in a 3D Tissue Scaffold toward a Comprehensive in Vitro Model for Breast Cancer Metastasis. ACS Appl. Mater. Interfaces, Dec 23;7(50):27810-22.
• Saha M, Kumar S, Bukhari S, Balaji SA, Kumar P, Hindupur SK, Rangarajan A. AMPK-AKT double negative feedback loop in breast cancer cells regulates their adaptation to matrix deprivation. Cancer Res. 2018 Mar 15;78(6):1497-1510.
• Saxena M, Balaji SA, Deshpande N, Ranganathan S, Pillai DM, Hindupur SK, Rangarajan A. (2018). AMP-activated protein kinase promotes epithelial-mesenchymal transition in cancer cells through Twist1 upregulation. J Cell Sci. 2018 Jul 26;131(14). pii: jcs208314.
• Andugulapati SB, Sundararaman A, Lahiry M, Rangarajan A. AMP-activated protein kinase promotes breast cancer stemness and drug resistance. Disease Models & Mechanisms. 2022 Jun 1;15(6):dmm049203.
• Warrier S, Srinivasan S, Chedere A, Rangarajan A. Inhibition of protein translation under matrix-deprivation stress in breast cancer cells. Frontiers in Medicine. 2023 Jun 22;10:1124514

PI: Annapoorni Rangarajan jointly with Srimonta Gayen

Impact of global warming on mammary gland development and stem cell biology

The mammary gland is a dynamic organ that develops significantly after birth. It undergoes morphogenetic changes at different developmental stages including puberty, pregnancy/lactation, and involution. These changes involve ductal elongation and branching, lobuloalveolar expansion, tissue remodeling and regression. Central to these developmental processes are the mammary gland stem cells (MaSCs) that possess the ability to self-renew and differentiate into various cell types.  MaSCs are crucial for the initial development, overall maintenance, and tissue regeneration during cycles of pregnancy and lactation during which they undergo extensive proliferation and differentiation. Mammary gland development also requires a high level of energy. The precise control of stem cell proliferation, differentiation and energy metabolism is crucial for ensuring proper tissue formation and function.

Increasing heat and climate changes are significant global concerns. Exposure to heat during pregnancy can adversely affect the mammary gland growth and function, leading to improper nourishment of the new-born and illnesses. This project aims to underscore the effects of heat-humidity stress on the mammary gland tissue architecture, stem cell biology, lactation, hormonal imbalance, bioenergetics and epigenetic alterations using mice models and human population study.

References-

• Dey D, Saxena M, Paranjape AN, Krishnan V, Giraddi R, Vijaya Kumar M, Mukherjee G, and Rangarajan A. (2009). Phenotypic and Functional Characterization of Human Mammary Stem/progenitor Cells in Long Term Culture PLoS ONE, 4(4):e5329.
• Paranjape, A.N., Mandal, T., Mukherjee G., Vijaya Kumar, M., Sengupta K. and Rangarajan, A. (2012). Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties. Oncogene, Apr 12;31(15):1896-909.
• Jinagal SL, Shekhar P, Chandra K, Mutnuru SA, Ramanan N, Foretz M, Viollet B, Bhat R, Rangarajan A. Prolactin-induced AMPK stabilizes alveologenesis and lactogenesis through regulation of STAT5 signaling. bioRxiv. 2022 Feb 16:2022-02.
• Mandal, S., Chandel, D., Kaur, H., Majumdar, S., Arava, M. and Gayen, S., 2020. Single-cell analysis reveals partial reactivation of X chromosome instead of chromosome-wide dampening in naive human pluripotent stem cells. Stem Cell Reports, 14(5), pp.745-754.
• Naik, H.C., Hari, K., Chandel, D., Mandal, S., Jolly, M.K. and Gayen, S., 2021. Semicoordinated allelic-bursting shape dynamic random monoallelic expression in pregastrulation embryos. Iscience, 24(9), p.102954.