PhD ADMISSION- 2024

1

Dr.Ananthalakshmy Sundararaman
Scientist C

1. Project Title: Mitochondria-derived Vesicles-Biogenesis and targeting in cardiac cells and its pathophysiological implications
Project Description: Ischaemia-Reperfusion Injury (IRI), where cellular dysfunction is exacerbated when blood flow is re-established, is the cause of further cardiomyocyte loss and organ failure after myocardial infarction. To limit the damage due to IRI our lab proposes to study the biogenesis of mitochondria-derived vesicles which play an important role in mitochondrial quality control and defense against oxidative stress induced during reperfusion. Targeting and improving mitochondrial damage repair mechanisms can keep the heart beating longer.
2. Project Title: Receptor trafficking deregulation in Oral cancer chemoresistance
Project Description: Surface proteomic approaches to identify differential surface expression of receptors in oral cancers that are chemo-naive and chemo-resistant will help identify receptors that aid cancers evade chemotherapy. The networks including metabolic regulators that enable this trafficking to happen will be studied along with small molecules that inhibit this surface population of receptors or their recycling to the surface thereby adding to the arsenal against oral cancer.

2

Dr.Anish Kundu,
Scientist C

Project Title: Elucidation of effectors from Pythium sp. associated with soft rot disease in Ginger
Project Description: Being a necrotrophic oomycete Pythium results in devastating soft rot disease in Ginger, though no specific effector molecule associated to Pythium infection is reported yet. We propose to identify the conserved effector molecule and its target through whole genome sequencing, transcriptome and proteome analysis.

3

Dr.Arun Sankaradoss,
Scientist C

1. Project Title: Characterizing humoral and cellular immune responses during viral co-infections.
Project Description: Viral co-infections are common in endemic regions like India and are recognized to influence clinical outcomes and transmission dynamics. Co-infections also serve as a mechanism for intra-host diversity, which can lead to genetic recombination and the emergence of new immune escape variants. These variants can affect the efficacy of vaccines and therapeutics. Thus, a detailed understanding of the cross-reactive B and T immune responses during viral co-infections in conjunction with genome sequencing is critical. The study aims to use flaviviruses (such as Dengue and Zika) and SARS-CoV as models to examine immune and genomic signatures during co-infections. 1. The study primarily employs in vitro and small animal models and system biology to define the molecular signatures of B and T cell responses. 2. The study also utilize NGS-based metagenomics to sequence viral genomes and investigate novel co-infections, if any, and their genetic diversity.
2. Project Title: Engineering circular RNA for enhanced translation efficiency in eukaryotic systems
Circular RNA (circRNA) has emerged as the new generation RNA modality for vaccine and gene therapy. Unlike linear mRNA counterparts, circRNA offers several advantages due to its closed confirmation, which protects it from exonuclease-mediated degradation. In addition, the half-life of circRNAs is 2.5 times longer than linear mRNAs, which could lead to prolonged expression of antigens. Considering these features, circRNA-based platforms may have superior application prospects in broad ranges of infectious diseases. However, the major challenge in using circRNA vectors for peptide or antigen delivery is their low transactional efficiency in eukaryotic systems. Thus, the study aims to optimize circRNA vector by employing various systemic approaches, i.e. optimization to vector topology, 5’ and 3’ UTRs, and internal ribosome entry sites (IRES). Further, the improved translational efficiency of circRNA will be investigated using in vitro and in vivo models.

4

Dr.Debanjan Bhowmik,
Scientist C

1. Project Title: Designing of biosensing and drug delivery platforms involving liposome/exosome coated nanoparticles.
Brief Description: Metal nanoparticles (NPs) can be easily made biocompatible. They come with a variety of shapes and sizes, have versatile surface chemistry, and possess unique optical properties. These characteristics have made metal NP-based nanoconstructs to emerge as attractive therapeutic, biosensing and imaging agents. Encapsulation of such nanoconstructs with liposome/exosome provide additional benefits. For example, exosome coating should enable better targeting (e.g., of cancer cells) with functional nanoconstructs, in vivo. On the other hand, encapsulation of metal-NPs with liposomes have allowed researcher to selectively probe lipophilic molecules by surface enhanced Raman spectroscopy (SERS).
In this project we plan to encapsulate metal nanoparticles with liposomes and exosomes. The exosome-coated nanoparticles will be developed as futuristic drug-delivery platforms. The liposome-coated nanoparticles will be integrated with anti-microbial peptide (AMP) based nanopores for SERS-based biosensing.
2. Project Title: Development of SERS and fluorescence-based biosensing platforms for probing exosomal cancer biomarkers.
Project Description: SELEX studies will be performed to identify the aptamers that can specifically target biomarkers of interest (e.g. exosomal HER-2). Chemically modified aptamers carrying fluorescence and/or Raman tags will be grafted on plasmonic nanoparticle surfaces. Raman and fluorescence spectroscopy-based experiments will be performed in the presence of the biomarkers to establish the techniques. The performance of the newly develop techniques will be tested against that of more established techniques like Western-Bolt, Immunolabeling, etc.

5

Dr.Debasree Dutta,
Scientist EII

Theme: Cancer Biology & Therapeutics
1. Project Title: Identification and targeting of epigenetic marks in distinguishing leukemia patients from normal healthy individuals.
Epigenetics drive the differential changes in the gene expression pattern in a normal vs healthy individual. Multiple epigenetic factors have been till date implicated in the incidence of leukemia. But the flow of events that give rise to the different epigenetic marks resulting from either signaling or epigenetic factors has remained unexplored. This understanding would culminate into a signature of marks that can distinguish between a leukemia vs normal healthy individual. In this study we aim to investigate the presence or absence of different histone epigenetics and DNA methylation marks in leukemia patient sample and healthy individuals. We would look into the functional importance of these marks in leukemia cell lines and using ChIP-seq and ATAC-seq would understand the role of these epigenetics marks in alteration of the chromatin.
2. Project Title: Characterization of the states of pluripotency in embryonic stem cells of different mammalian species
It is known that embryonic stem cells (ESCs) from different mammalian species exhibit different states of pluripotency in the continuum of development. It basically depends on the media which is being used to derive the ESCs. However, recent studies from our lab and other research groups have established multiple states of pluripotency in embryonic stem cells. But, does these states indicate the difference in development of different mammalian species. The proposed study would look into this by considering murine, rat, bovine and human ESCs and the pre-and post-implantation development using blastoid and gastruloid model systems. We will also explore how a cohort of transcription factors and signaling mechanisms dictate different states of pluripotency among different mammalian species using Next-generation sequencing at single cell level.

6

Dr.Devasena Anantharaman
Scientist F

Project Title: Characterization of genomic and transcriptomic profile of oral cancers to predict chemotherapy response.
Project Description: Oral cancer is among leading malignancies in India. Majority of oral present in locally advanced stages and often require multi modality treatment including chemotherapy. Treatment decision making is heavily dependent on clinical stage, although its ability to predict patient prognosis is limited. While it is well known that patients demonstrate variable response to the available chemotherapy regimens; the molecular bias for this variation remains largely unknown. Using large scale data analysis tools the present project aims to unravel the genomic and transcriptomic underpinnings of chemotherapy resistance in oral cancer.

7

Dr.K B Harikumar,
Scientist E II

Project Title:Tumor microenvironment mediated resistance to cancer cell surface targeted therapeutics in pancreatic cancer
Project Description:Tumor microenvironment that constitutes stromal cells, immune cell
components, tumor associated fibroblasts, endothelial cells of blood vessels etc are important in the tumorigenesis process. Recent studies suggest that they also modulate the tumor cells response to chemotherapeutics in multiple ways. Currently tumor cell surface targeted drugs and biologicals are being evaluated as potential cancer specific interventions. The study is proposed to understand how TME regulate tumor resistance against such new generation drugs in pancreatic cancer model.

8

Dr.Karthik Subramanian,
Scientist C

Project Title: Investigation of mechanisms underlying pneumococcal bacteria adaptation to intracellular survival within host immune cells.
Project Description: Streptococcus pneumoniae is a major human respiratory pathogen that normally colonizes the upper respiratory tract in young children below 5 years and causes life-threating infections such as pneumonia, septicemia and meningitis. Recently, macrolide antibiotic resistant S. pneumoniae strains has been classified as medium priority amongst the top 15 pathogens that are most threatening to human health (WHO, 2024). We have previously discovered that pneumococcal bacteria can live an intracellular lifestyle within lung macrophages and dendritic cells by hijacking host receptors for cellular invasion (Subramanian et al., Nature Microbiology. 2019). However, the mechanisms behind how the intracellular bacteria modulate host gene transcription to evade immune killing are unclear. In this project, we will employ GFP-based FACS sorting of infected cells and multiomics approaches (transcriptomics, proteomics) to investigate mechanisms contributing to bacterial persistence within immune cells and immune evasion.

9

Dr.Karthika Rajeeve,
Scientist EI

Project Title: Developing human lung organoid model to study Mycobacterial pathogenesis
Project Description: Tuberculosis (TB) caused by the intracellular pathogen, Mycobacterium tuberculosis (Mtb), infects nearly 10 million people annually. Despite being preventable and curable, 1.5 million people die from TB each year. India holds the largest share of global burden (31%of the total TB death). On invading the host, Mtb is phagocytosed by macrophages as a part of host defense. The bacilli hijack and reprogram the macrophages as “Trojan horse” and remain persistent or dormant. With favorable conditions, the bacterium reactivates resulting in active TB. The study in our lab is focused on investigating the mechanism of dormancy and reactivation using human lung Organoid. This will offer new avenues for fundamental and therapeutic research.

10

Dr.Kathiresan Natarajan,
Scientist C

Project Title: Unravelling the role of α7-nAChR in pathophysiology of cardiovascular diseases
Project Description: Targeting α7 nicotinic acetylcholine receptors (nAChRs) in cardiomyocytes could be a potential therapeutic strategy for treating cardiovascular diseases by improving heart function and preventing heart failure or arrhythmia progression. Studying α7-nAChR -mediated signaling pathways could enhance understanding of cardiovascular diseases and aid in the development of cardioprotective agonists.
Objectives include: 1. Calcium binding site mutagenesis and developing agonist/antagonist to regulate α7-nAChR activity.
2. Relationship between α7-nAChR mediated calcium signalling and cardiovascular diseases.
3. SiRNA-mediated α7-nAChR mRNA silencing to analyse involvement of apoptotic and ferroptosis pathways.
4. Overexpression studies of α7-nAChR to identify their role in inflammatory signalling pathways.
5. Drug screening against heart failure using α7-nAChR as a target in mouse models.

11

Dr.Leny Jose,
Scientist EI

Project Title: Developing in vitro DNA damage models that closely mimics viral infection.
Project TitleDescription: Viral infection has been recently shown to elicit DNA damage in infected cells, mice and patients. The DDR response is followed by induction of pro-inflammatory cytokines and ultimately leads to cell senescence. A specific subset of co-infecting pathogens can utilize this genomic instability inside the cell to establish themselves inside the host cell. For e.g., human papillomavirus replication can cause altered DDR in infected cells allowing them to proliferate and become malignant. The study will use DDR models to study host pathogen interactions.

12

Dr.Lightson N G,
Scientist C

Project Title: Study of Antimicrobials Against Pathogens on High-resolution Bioassay Platform
Project Description: The global health burden due to antimicrobial resistance (AMR) and its associated problems is an ever-increasing and alarming concern, and it is imperative to call for action to avert a developing global healthcare crisis. To combat this global multifaceted phenomenon, one of the approaches is developing different novel antimicrobials. In conjunction with this, we plan to study and analyze antimicrobials against pathogens using interdisciplinary advanced techniques to understand different bio-physical phenomena. Different biophysical studies and evaluations of membrane permeability will be conducted using fluorescence assays in microfluidic platforms. Such studies would better understand the cellular and molecular behavior and properties of the membrane pores, which would be useful information for designing, synthesizing, and engineering antimicrobial agents.

13

Dr.Mahendran K R,
Scientist E II

Project Title: Building unnatural peptide pores targeting bacterial membranes against antibiotic resistance.
Project Description: We propose using frog peptides as potential antimicrobial peptides (AMPs). Reconstituting these peptides into planar lipid bilayers and liposomes will enable their structural and functional characterization. We suggest that engineered mirror image peptides will be highly resistant to protease degradation and exhibit enhanced membrane disruption activity. Finally, microbiology and cell permeation assays will be performed to evaluate the antimicrobial activity of pPorA against several bacteria. The inhibitory effect of the peptides on bacterial biofilm formation will be determined. We emphasize that our project addresses the critical question of how antimicrobial peptides exert their action on bacterial membranes, which would help us develop peptide-based therapeutics.

14

Dr.Moumita Srivastava,
Scientist C

Project Title: Identification and functional characterization of post-translational modification machinery involved in plant-pathogen interaction
Project Description: We aim to identify the post-translational modification (PTM) machinery in both plants as well as pathogens. Our lab is very much focused to utilise the potential of PTM machinery as a tool to enhance the plant resilience against biotic stresses, particularly Phytophthora capsici as well as Botrytis cinerea. We employ a wide range of techniques, including proteomics, genomics, biochemistry, gene editing (CRISPR), live cell imaging, and bioinformatics, to address these questions. The project will utilize both model plants (Arabidopsis) as well as crops (black pepper) to elucidate the mechanism.

15

Dr.Nagarjun Narayanaswamy,
Scientist C

1. Project Title: Development of DNA-based fluorescent probes for pathogen detection on biosensor platforms
Project Description: The Gram-positive bacteria, Streptococcus pneumoniae cause severe invasive and non-invasive diseases in children and adults and also can persist in the nasopharyngeal mucosa of healthy carriers without causing clinical manifestations of the infection. More than 90 pneumococcal serotypes have been identified based on the structurally different capsular polysaccharides (CP) expressed by S. pneumoniae. Lack of sensitive and rapid diagnostic technologies are major bottleneck in treating and preventing disease spread. Increasing antimicrobial resistance is a worldwide problem that needs advanced and preferably portable multiplexed diagnostics for sensitive detection and characterization of different bacterial serotypes. The project aims to design and develop validated DNA-based fluorescence pattern ID probes for the multiplex detection of different serotypes of S. pneumoniae in biological samples towards this end.
2. Project Title: Understanding the role of Mitochondrial stress induced ferroptosis cell death in cardiovascular diseases
Project Description: Ferroptosis is a unique form of programmed cell death driven by iron-dependent lipid peroxidation and implicated in various cardiovascular diseases (CVD). Recent evidences suggest that the misregulation of Iron homeostasis is one of the major risk factors in cardiac functions. Therefore, it is essential to understand how the regulatory pathways of Iron metabolism and ferroptosis cell death in cardiomyocytes are linked to disease manifestation of cardiovascular diseases. To address this, we will develop triphenylphosphonium cation (TPP+) linked radical trapping agents (mRTAs) to specifically target the mitochondria and gain insights into how mitochondrial iron metabolism and oxidative stress modulate ferroptosis cell death in cardiomyocytes and in vivo animal model.

16

Dr.Pallabi Mitra,
Scientist C

Project Title: Elucidating the molecular basis for Toxoplasma gondii survival and multiplication in the host, mediated through host-parasite cross-talk
Description: Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Other members of this phylum include the human pathogens Plasmodium and Cryptosporidium. Toxoplasma gondii is an extremely successful zoonotic parasite that causes lifelong chronic infections in almost all warm-blooded animals, including humans, and severe disease in foetuses and immunocompromised individuals. There is no human vaccine, and the few available drugs have serious side effects and are ineffective against chronic-stage disease.
This project aims to understand the molecular basis of how Toxoplasma co-opts the host signaling pathway to grow and multiply within a host cell. Our recent study has already provided valuable leads indicating a pivotal role of the host stress signaling pathway in intracellular parasite propagation (Mitra et al., BBAMCR, 2020). The study reveals significant host-pathogen crosstalk essential for parasite multiplication and survival, which we would like to investigate further. To this end, we will use protein biochemistry, high-resolution imaging, CRISPR based gene manipulation techniques, and high throughput omics approaches to uncover the molecular mechanism underlying the host-parasite interaction. Given the parasite's ubiquitous nature, we are also interested in exploring the exciting area of co-infection with other widely distributed pathogens of interest in the light of this cross-talk.

17

Dr.Parijat Senapati,
Scientist C

Project Title: Role of KRAB-ZFP proteins in cancer stem cells
Project Description: Cancer stem cells (CSCs) show high levels of plasticity which are attributed to epigenetic events that enable the fast acquisition of traits supporting adaptation to changes within the cancer environment. Krϋppel-associated box domain zinc finger proteins (KRAB-ZFPs) are the largest family of transcriptional repressors responsible for epigenetic silencing of retrotransposon elements and genes. KRAB-ZFPs are expressed in the developing embryo as well as in embryonic stem cells where they are known to regulate pluripotency and stemness. KRAB-ZFPs have also been shown to regulate CSC identity and CSC properties, however, the mechanisms are not well understood. This project will involve identifying and characterizing KZFP proteins that regulate CSC properties such as stemness, self-renewal, differentiation leading to recurrence and chemoresistance. Functional studies involving CRISPR KO and CUT&RUN/ChIP-exo studies in in vitro cell line and orthotopic mouse models will be used to identify the mechanism and functional role of individual KZFP protein in regulating cancer stem cell properties.

18

Dr.Ramesh Pothuraju,
Scientist C

Project Title: Gum acacia dietary fiber preventive effects on obesity mediated colorectal cancer
Project Description: Dietary interventions are increasingly recommended to mitigate the prevalence of obesity and its associated cancers, with a particular focus on fibers as potential therapeutic agents. Dietary fiber defined as the indigestible portions of plant foods by human digestive enzymes and is fermentable by the gut microbiota in the colon. Among the various naturally occurring fibers “Gum acacia” (GA) stands out as a natural gummy and its role on CRC in obesity are largely unclear. The proposed research is novel in its specific exploration of dietary fiber GA impact on obesity associated CRC.

19

Dr. Rashmi Mishra,
Scientist E-II

Project Title: Project Title: Investigating the Role of SUMOylation and Glycosylation in Oral Cancer Diagnosis, Prognosis, and Chemo-Therapeutics.
Project Description: Oral cancer is a significant global health concern, characterized by a high incidence and mortality rates. Poor prognosis for oral cancer patients is often due to late-stage diagnosis and resistance to traditional treatments. Post-translational modifications (PTMs) like SUMOylation and glycosylation play crucial roles in cancer biology. However, their specific impact on oral cancer progression and recurrence remains understudied. This proposal aims to explore the combined roles of SUMOylation and glycosylation in oral cancer diagnosis, prognosis, and response to chemotherapy. Leveraging state-of-the-art investigational techniques and our highly collaborative in-house team's expertise in clinical and animal model research, our work will have profound clinical implications not just for oral cancer diagnosis and treatment but for other cancers that relyon SUMOylation and glycosylation for survival and fitness.
Project Title: Project Title: Targeting the Plasma Membrane in the Pathogenesis of Aggressive Cancers of Breast and Brain for Effective Diagnosis and Chemo-Therapeutics.
Project Description: Aggressive and fatal cancers affecting the breast and brain, such as triple negative breast cancer and glioblastoma multiforme (GBM), present significant challenges due to their rapid progression and resistance to standard treatments. The progression of aggressive cancers relies on the cancer cells' ability to quickly adapt to their harsh microenvironment. Since the plasma membrane is the primary interface through which the microenvironmental stress is detected and the adaptation to the microenvironment is initiated, the modified plasma membrane of cancer cells is expected to play a crucial role in the origin, progression, and resistance to treatment of the disease. This makes plasma membrane a promising target for new diagnostic and therapeutic strategies. This proposal aims to use mass spectrometry-based omics analysis, advanced flowcytometry, microfluidics, 3D cell cultures, animal disease models, and super-resolution confocal imaging to (i) investigate the molecular mechanisms underlying thealterations in the plasma membrane of aggressive breast and brain cancers and (ii) use the findings to develop innovative approaches for diagnosis and targeted chemotherapy to improve

20

Dr.S Asha Nair
Scientist G

Project Title: Lactoferrin Micro/Nanoencapsulates Inhibits Inflammatory Induced Colorectal Cancer, And Enhanced Immune Response Via Gut Microbiome Alterations
Project Description: Lactoferrin, an iron-binding glycoprotein from milk, plays roles in iron absorption, immune response, anti-inflammation, and anti-carcinogenesis. It mediates signals between gut microbiota and intestinal immune cells. The GI tract, crucial for nutrient digestion, immune cell positioning, and microbial colonization, can trigger inflammatory responses when imbalanced. Disease-related immune deficiencies, linked to gut microbiota changes, can be managed through dietary interventions. This study aims to develop lactoferrin micro/nanoencapsulates with dietary fibre for gut-linked immunomodulation, enhancing lactoferrin transport and absorption across the gastrointestinal barrier, offering an oral delivery alternative to systemic therapy as an anti-inflammatory, anti-proliferative and immune stimulant.

21

Dr.Shijulal NS,
Scientist E-I

Project Title: Discovery of novel biomarkers for bacterial pathogen detection and resistance level estimation using S. aureus
Project Description: Antibiotic resistance in priority pathogens is one of the global threats. Gram-positive bacterial pathogens such as Staphylococcus aureus are a leading cause of numerous illnesses ranging from food poisoning to life-threatening diseases. The resistance pattern of S. aureus varies significantly across strains and subtypes. The project aims to identify novel biomarkers for detecting resistance strains of S. aureus using the genomic and expression data with the support of ML techniques. The predicted biomarkers will be subjected to validation. Based on the identified markers, microfluidic fluorescence-based probes will be developed for the identification of multidrug-resistant strains of S. aureus.
Project Title: Modelling of the pore-forming peptides in the bacterial membrane environment
Project Description: Antibiotic resistance in pathogenic bacteria is a global threat. Antimicrobial peptides (AMPs) have gained significant attention due to their antimicrobial activity against a broad spectrum of Gram-negative and Gram-positive bacterial pathogens. However, understanding the mechanism of action of AMPs still remains a challenge. Here we will perform computational screening of distinct AMP libraries against Gram-Positive bacterial pathogenic bacterial targets. Membrane response to peptide binding will be investigated under different conditions (such as temperature, ions, membrane components, and peptide concentration, etc). And use advanced computational techniques to model the peptide structures and all-atom (AA) and coarse-grained (CG) molecular dynamics (MD) simulations to provide molecular-level insights into the pore-forming process. In addition, these peptides will be studied its capability to form efflux pump inhibitors.

22

Dr.Sunil Martin,
Scientist E-II

Project Title: Affinity modulation of antigen binding domains to enhance the efficasy of CAR T cells

23

Dr.Tessy Thomas Maliekal,
Scientist E II

Project Title: Evaluation of the functional Impairment of TIF1g modulating oral cancer recurrence.
Project Description: TIF1g is a E3 ubiquitin ligase that can act both as tumor suppressor and tumor promoter. The study will be designed to assign the domain of the molecule that regulate each function. The functional significance of the mutations present in oral cancer samples will be evaluated for its role in the regulation of recurrence.