Prospective PhD projects

Faculty in MRDG who would be interested in PhD students this year are as follows:

Arun Kumar

The research interests of my laboratory, in a broad sense, lie in the area of Human Molecular Genetics and Cancer Biology. Currently, we are looking for motivated student(s) to work on any one of the following projects.

Project 1-Identification of TSC2-regulated protein coding and non-coding genes: Mutations in tumor suppressor TSC1 and TSC2 genes cause an autosomal dominant disorder, tuberous sclerosis complex (TSC). TSC1 and TSC2 proteins interact to form a complex, which negatively regulates mTORC1 in the PI3K-AKT-mTOR pathway, and in turn regulates cell proliferation. This is a well-known cytoplasmic function of these TSC genes. We and others have shown earlier that TSC1/hamartin localizes to the cytoplasm, whereas TSC2/tuberin shows nuclear as well as cytoplasmic localization. To elucidate the nuclear function of TSC2, we have used gene expression profiling of TSC2-overexpressing cells, luciferase reporter assay, siRNA knockdown, ChIP and EMSA techniques, and have shown for the first time that TSC2 also functions as a transcription factor and transcriptionally regulates Epiregulin, a ligand for EGFR. However, Epiregulin cannot be the only TSC2-regulated gene. Then, what are the other genes regulated by TSC2? The interested student(s) will thus explore and identify other (protein coding & non-coding) genes, which are transcriptionally regulated by TSC2, using a variety of molecular and cell biology approaches such as microRNA microarray analysis and RNASeq. The work will also involve the exploitation of TSC2-regulated gene(s) in oral cancer therapeutics.

Project 2-Molecular consequences of mutations in ATP7B, coding for a copper transporter: Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ATP7B, which codes for a trans-Golgi network residing copper transporter. We have recently performed the genetic analysis of 102 WD families from a south Indian population, and identified 36 different ATP7Bmutations, including 13 novel ones. However, the molecular consequences of these novel mutations in disease pathology are not known. Using a variety of molecular and cell biology approaches, the interested student(s) will explore and identify the role of these novel ATP7B mutations in disease pathology. The work will also involve the use of specific inhibitor(s) to restore the function of mutated ATP7B, with an aim to develop therapeutic treatment for WD.

Sona Rajakumari

Adipocytes are key players in energy homeostasis and are categorized into two major types: white and brown adipose cells. White adipose tissue stores energy and expands during obesity. Brown adipocytes and brown fat-like cells (beige fat) reside within white adipose tissue undertake high turnover of β-oxidation and release energy as heat through uncoupled respiration. This unique property of brown and/or beige adipocyte promotes energy expenditure, improves insulin sensitivity and protects animals against metabolic disease. Although beige and brown adipose cells execute similar functions, it is unclear whether brown and beige adipose stem cells are derived from a common progenitor cell or arise independently during development. Our lab is interested in studying the molecules and pathways that regulate the specialization of white, brown and beige fat prior to or during their differentiation.

The following are major research projects

(a) Transcriptional regulation of Brown/Beige fat development in mammals.

(b) Identify and study the signaling pathways that control brown fat development and function.

(c) Understand the role of physiological cues such as age and obesity on adipose stem cell maintenance or its efficiency.

Upendra Nongthomba

Students interested in pure genetics-based research using fruitfly model may contact Prof Upendra Nongthomba for prospective research projects.

Ramray Bhat

We are broadly interested in understanding how cancers invade and metastasize to different parts of the body. Using experimental, bioinformatica and theoretical approaches, we focus on the cues from the stroma: cells, proteins and sugars that may be involved in this process in breast and ovarian cancer. The incoming student will be encouraged to frame her or his research questions on this topic in relation to the changed metabolic regulation within cancer epithelia.

Varsha Singh

A. Microbe Pattern recognition in C elegans: Sensing of bacterial volatiles by host sensory neurons drives calcium signaling resulting in chemotaxis response of C elegans to pathogens. Pseudomonas aeruginosa and Klebsiella pneumoniae will be used as pathogens.

B. Infection induced lipolysis: we have recently found that C  elegans utilizes neutral lipids stored in the intestine to fuel innate immune response, a process  termed “infection induced lipolysis”. In this project, we will investigate if sensory neurons control lipolysis occurring  during infection with Gram positive and Gram negative bacteria. Single cell ablation lines of C elegans generated in the lab and other transgenic strains will be used for studies.

Techniques used for A an B: Molecular biology, RNA interference, rna-seq and qPCR, chemotaxis assays, survival assays, GC-MS-MS, lipid analysis, transgenesis in C elegans using CRISPR CAS, GCaMP based assays in C elegans neurons etc.