Prospective Students

The following faculty are planning to take Ph.D. students in 2024 (for interviews held in May 2024).

Prof. Annapoorni Rangarajan

Molecular mechanisms of cancer stemness and drug resistance
Cancer stem cells (CSCs) are a rare sub-population of cancer cells identified within several cancers that possess properties of normal stem cells such as self-renewal and the ability to give rise to diverse cell types. These properties of CSCs also contribute to cancer heterogeneity and disease complexity resulting in metastasis, drug resistance, and disease relapse. Therefore, understanding the mechanisms of cancer stemness and drug resistance is of utmost importance to improve treatment outcomes.

Epithelial to mesenchymal transition (EMT) is a developmental programme hijacked by cancer cells and is considered to be a pre-requisite for cancer spread by metastasis. Prior work in AR lab has identified the energy sensor kinase AMPK as a central player contributing to EMT, stemness and drug resistance phenotypes, thereby aiding metastasis. This study will aim to understand the role of AMPK in EMT during normal embryonic development and cancer metastasis using Drosophila, mouse models, and human cancer cell lines.

References-
• 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. doi: 10.1158/0008-5472.CAN-17-2090.
• 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. 

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Prof. Deepak K Saini

Details to be provided soon. Meanwhile, please check faculty home page.

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Dr. Meetali Singh

Parasite Epigenetics Lab
Lab website: www.meetaliLab.com
Twitter: @meetalichauhan

meetalisingh@iisc.ac.in

RNA interference (RNAi) is a conserved pathway across all eukaryotic species, with a notable exception of some parasitic protozoa, including Plasmodium falciparum. On the other hand, protozoan parasites like Toxoplasma, Trichomonas, and Trypanosoma, among others, retained RNAi, however, with minimal components and RNAi factors with atypical domains. Our understanding of RNAi (small RNA) pathways in most of these organisms is very limited. In this proposed study, we will investigate the functions of this minimal RNAi pathway using Toxoplasma gondii as a model system. Toxoplasma gondii can infect any nucleated cell in warm-blooded animals, where it reproduces asexually, with the sexual cycle taking place in the definitive hosts of the cat family. Despite a minimal RNAi pathway, deep sequencing has identified small RNAs in Toxoplasma gondii. Yet, their function in the life cycle and pathogenesis of the parasite is entirely unknown.

To address the big question of how this atypical small RNA pathway mediates epigenetic regulation of pathogenesis and host-parasite interaction, we will implement the following projects using state-of-the-art methods, including Next-Gen sequencing methods (Illumina and nanopore platform), proteomics (Mass-spec), molecular biology, biochemistry, and computational data analysis.:

1. ​Understanding the role of a minimal small RNA pathway in the intracellular survival and stage transition of the parasite Toxoplasma gondii
2. ​Understanding RNAi evolution: What are the minimal and atypical factors and the biogenesis of small RNAs?
3. Understanding the cross-talk of the host and the parasite’s small RNA pathways & crosstalk with other epigenetic mechanisms

If you would like to explore the world of small RNAs with us, visit our lab (GB-01) during the interviews while you are in Bangalore.

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Dr. Nikhil Gandasi with Prof. Deepak K Saini (Joint student)

Dr. Sona Rajakumari

The research program in our laboratory focuses on key transcription factors and lipid molecules that regulate adipose tissue development, function, and maintenance of pre-adipose stem cells under various metabolic conditions, including diet-induced obesity, aging, type 2 diabetes etc. To address our research hypothesis, we employ several cutting-edge approaches, including CRISPR-Cas9 mediated gene editing, transcriptomics, lipidomics, and tissue-specific or transgenic mouse models.
References:
1. 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.
2. Shapira SN, Lim HW, Rajakumari S, Sakers AP, Ishibashi J, Harms MJ, Won KJ, Seale P. (2017). EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex.
Genes Dev. 31(7):660-673.
3. 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.

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Prof. 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 processes involved, using molecular biology, biochemistry, and structural biology techniques (Cryo-electron microscopy and X-ray crystallography). Facilities for cryo-EM and X-ray crystallography are available in IISc.

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

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Prof. Upendra Nongthomba

Details to be provided soon. Meanwhile, please check faculty home page.

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Prof. Annapoorni Rangarajan and Dr. Srimonta Gayen (Joint)

Epigenetic mechanisms have emerged as key players in the regulation of cancer cell-states such as matrix-attached vs detached, stem vs non-stem, EMT vs MET that contribute to cancer heterogeneity and therapy failure. In this study we will explore epigenetic mechanisms such as histone modification, DNA methylation, and X-chromosome re-activation (XCR) in the regulation of cancer cell plasticity by employing ChIP sequencing and transcriptomics approaches. This study will be undertaken jointly with Dr. Srimonta Gayen.

• 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., Jolly, M.K. and Gayen, S., Single-cell analysis reveals X upregulation is not global in pre-gastrulation embryos. Iscience,25(6), p.104465.
• Naik, H.C., Hari, K., Chandel, D., Mandal, S., Jolly, M.K. and Gayen, S., Semicoordinated allelic-bursting shape dynamic random monoallelic expression in pregastrulation embryos. Iscience,24(9), p.102954.

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