PhD ADMISSIONS – January 2024

1.

Dr. Debasree Dutta

Scientist E II

Targeting epigenetics in devising tools to understand and address developmental disorders or diseases.

Studies from our lab have demonstrated that chromatin modifying factors called histone chaperones, could influence mammalian development and could regulate the fate of diseases. These findings have led to the identification of histone chaperones that could be evaluated as biomarkers for diseases including pre-eclampsia and breast cancer. With models based on stem cells (Embryonic stem cells/iPSCs), blastoids, gastruloids, mice, cell liines and human samples, we will understand how these molecules that regulate epigenetics would help in devising tools to study and treat diseases. In that pursuit, we will exploit chromatin based molecular techniques including qChIP, ChiP-seq, DNase HS mapping, ATAC-seq among others. The functional studies would be done with gene specific knockdown or knockout in the models described above.

2.

Dr. Jackson James

Scientist -G

Development of a microchip for detection and confirmation of neurodegenerative and neuro-developmental disorders.

3.

Dr. Karthika Rajeeve

Scientist E1

Investigating the mechanism by which Chlamydia trachomatis evades host immune response.

Sexually transmitted infections (STI) remain a major societal and economic burden despite public health initiatives, vaccinations, and the development of antibiotics. There are estimated to be 357 million new cases of STIs annually, out of which Chlamydia trachomatis (Ct) stands first, infecting 131 million people every year worldwide and in India it is underestimated and is considered as a national burden. To date not much is known about how the pathogen remains hidden and undetected by the host immune system. The type of cells that the bacteria infect the uterus also remains unknown. Although Chlamydia is known to harbor the genital tract, it has been strongly associated with reactive arthritis, and very recently scientists have also discovered a reservoir of this bacteria in the intestinal tract, the path of this dissemination also remains unknown. In this study, we plan to investigate the molecular mechanism by which the bacteria evades the host's immune response.

4.

Dr. Karthik Subramanian

Faculty Scientist-C, Pathogen Biology

Project: Investigating adaptation of pneumococcal pathogen to intracellular survival and modulation of host responses

Synopsis: We have recently discovered that pneumococcal bacteria can live an intracellular lifestyle within lung macrophages and dendritic cells by hijacking host receptors (Subramanian et al., Nature Microbiol. 2019). However, the mechanisms behind how the intracellular bacteria modulate host gene transcription to evade immune killing are unclear. Main aims of this project are:
1. Flow sorting of human cells infected with fluorescent-tagged bacterial strains
2. RNA sequencing to identify host genes regulated by intracellular pneumococci.
3. Dynamics of bacterial dissemination from intracellular to systemic infection using mouse models.

5.

Dr. Kathiresan Natarajan

Scientist C

Unraveling the role of alpha7-nAChR mediated Calcium Signaling in Neuronal Apoptosis

Apoptosis shapes the growing brain and neuronal death occurs in many human neurological disorders. The pathogenesis of both acute and chronic neurodegenerative diseases has been linked to programmed cell death (PCD). The mechanisms behind α7-nAChR neuroprotective effects are yet unknown, although they may involve regulation of both survival and apoptotic signaling pathways. Understanding the biochemical and molecular changes that cause neuronal cell death and neuroprotective effect of α7-NachR signaling may soon lead to effective preventative and therapeutic approaches. In this study, we will examine the role of caspase dependent and independent PCDs, as well as pro-survival pathways in response to α7-NachR mediated calcium signaling.

6.

Dr. K R Mahendran

Scientist E1

Conformational Flexibility Driving Antibiotic Translocation Across Bacterial Transporter

Bacterial outer membrane pores typically restrict the translocation of large molecules and the molecular mechanism underlying this process remains elusive. Here, we investigate a rare bacterial membrane transporter comprising a charged zone and a constricting segment involved in the selective uptake of unusually large cyclic sugars. Our study contributes novel insights into energy-independent membrane transport mechanisms of large substrates, including antibiotics and would aid the development of potential blockers against multi-drug resistant bacteria.

7.

Dr. Lightson N G

Scientist C

"Hybrid Nucleic Acid Aptamer - Molecularly Imprinted Polymer System for Bio-Molecular Recognition"

Nucleic acid aptamers (NAAs) and molecularly imprinted polymers (MIPs) have individually shown potential applications in both diagnostics as well as therapeutics. In this work, novel hybrid systems (NAA-MIP) will be engineered to develop high-performance bio-molecular recognition elements. The study will investigate different features such as (a) high binding affinity (nM to pM), (b) high sensitivity and selectivity (nM to fM), and (c) high stability (days to months).

8.

Dr. Nagarjun Narayanaswamy

Scientist-C

Activity-based fluorescent tools for monitoring Protein post-translational modifications

Brief description: Lysine acetylation is one of the major post-translational modifications of proteins and it is a key regulator for diverse cellular processes. The initial research on lysine acetylation was predominantly focused on the nucleus, where it regulates histone biology and transcription. Recent advanced mass spectrometric tools have revealed the presence of lysine acetylation in most intracellular organelles and it is crucial for cell function and homeostasis. However, there are no available live fluorescence imaging tools for lysine deacetylases (KDACs) in living systems. In this context, we will develop a new class of activity-based fluorescenceprobes for imaging KDACs and study their activity in subcellular compartments in a spatiotemporal manner. Further, we are interested in understanding the role of lysine modifications in metabolic disorders.

9.

Dr. Rajesh Chandramohanadas

Scientist E-II

Title: Dissecting Host Protein Import Mechanisms in Plasmodium spp.

Plasmodium falciparum, the causative agent of human Malaria, recruits certain host proteins to substitute (or complement) its own oxidative defence system. This not only allows full exploitation of the host components, but also conserves metabolic reserves of the parasite for synthetic purposes. However, from a mechanistic viewpoint, evidence for vesicular trafficking or other membrane transport processes in iRBCs to facilitate selective protein intake is lacking, other than for haemoglobin catabolism. Furthermore, it remains to be determined whether host proteins are actively hijacked by the parasite or it represents an apparently passive host response to control and minimize the damage caused by infection. This project is an effort towards clarifying ambiguity around this process and to establish beyond doubt that host protein import/uptake is a specific active process, likely mediated by the infectious agent.

10

Dr. Rashmi Mishra

Scientist EII

1) Project 1: Understanding the role of SUMOylation in microenvironmental stress sensing and response in cancers: From discovery to translation.

2) Project 2: Multi-omics assisted exploration of the cell plasma membrane dynamics: Novel insights towards therapeutics of aggressive cancers and neuro-cardio-degenerative conditions.

11.

Dr. Shijulal N S

Scientist C

This bioinformatics laboratory is mainly focused on a better understanding of the emergence and evolution of antibiotic resistance as well as the development of strategies to combat AMR within Gram-positive priority pathogens using S. aureus as a model. This term, one project is offered from each category.

1. Reconstruction of evolutionary trajectories of antibiotic resistance in priority bacterial pathogens (Evolutionary Bioinformatics)
A major challenge in the near future will be to tackle the evolution of resistance to novel classes of antibiotics in bacterial pathogens . The emergence of antibiotic resistance mechanisms and its spread maintained in a population of bacteria is determined by the interplay of several basic factors, such as mutation rate, level of resistance conferred by the resistance mechanism, fitness of the antibiotic-resistant mutant bacteria as a function of drug concentration, and strength of selective pressures. Genetic factors responsible for resistance against most classes of antibiotics have been discovered in the gut, environmental microbiome, and even geographic locations thought unlikely to have ever been exposed to human sources of antibiotics. However the ability to predict the probability of ‘Gene transfers’ leading to antibiotic resistance in bacterial pathogens is still lacking. The proposed project utilizes bioinformatics techniques coupled with experimental evolutionary studies (omics approaches) to better understand the emergence and evolution of antibiotic resistance in Gram-positive bacterial pathogens.

2. Discovery of phytochemical small molecule synergies to combat antibiotic resistance in priority pathogens
The bacterial pathogens are becoming multi-drug resistant, and new approaches are becoming essential to combat the antimicrobial resistance within bacterial pathogens. Traditional knowledge and medical plants remain an underexplored repository of bioactive compounds. Advanced computational techniques coupled with experimental approaches can be used to guide future research efforts on tackling amr in bacterial pathogens. Using a muti-disciplinary approach (Datamining, Structural bioinformatics & Microbiology techniques) the proposed project aims to (i) Identify and validate novel drug targets for antimicrobial agents within Gram-Positive priority pathogens (ii) develop novel methodologies (ML-based) to predict molecules that can have synergy between phytochemicals and small-molecules upon its action (iii) Discovery of antibacterial compounds and validation of the effect of synergies.