Biosciences

Antimicrobial Resistance
The AMR laboratory is dedicated to understanding the fundamental principles involved in the acquisition of antimicrobial resistance determinants and their dissemination among clinically relevant pathogenic bacteria. We apply this knowledge to develop tools for rapid, point-of-care diagnostics to support bedside treatment of drug-resistant bacterial infections.

Our approach is multidisciplinary and collaborative, encompassing wet lab research, whole genome sequencing, Artificial Intelligence (AI), Machine Learning (ML), and biostatistical tools to understand the emergence of antimicrobial resistance. Furthermore, we are developing prediction models for the rapid diagnosis and prediction of bacterial infections.

Additionally, we have a state-of-the-art AMR biorepository with 4000 clinically isolated bacterial pathogens and a dedicated cell culture facility to support host-pathogen interaction studies. Our research is supported by national and international collaborations with academic institutions, research institutes, hospitals, and industries.

DISEASE BIOLOGY

Protein Aggregation Diseases
In Huntington’s Disease (HD)
We have demonstrated using multimodal MRI that changes in brain volume, fractional anisotropy, apparent diffusion coefficient, metabolic changes, and glucose utilization precede the onset of symptoms. Further, using metabolomic analysis we have demonstrated the deregulation of metabolic pathways in pre-symptomatic and symptomatic patients which overlap with deregulated metabolic pathways in the yeast model of HD. Using metabolic addition and gene knock-out experiments we have demonstrated that these pathways modulate mutant aggregation in yeast models of HD. B6, B12, and folate could mitigate mutant Huntington aggregation potentially by modulating deregulated metabolic pathways. Our results show that early intervention during the pre-symptomatic stage in genetically susceptible individuals by maintaining metabolic homeostasis might help in better management of the disease.

In Amyotrophic Lateral Sclerosis (ALS)
Using publicly available data sets we showed oxidative phosphorylation as a common deregulated pathway across data sets. Further, using the yeast model of ALS we demonstrated complex III and IV modulated aggregation of wild-type and mutant FUS and TDP43 with implications for disease. The addition of metabolites from deregulated pathways like Glutathione, short-chain fatty acids, and Nicotinic acid cleared TDP-43 aggregates. Ginseng and its component flavonoids and Ginsenosides could clear FUS/ TDP-43 aggregates.

In Alzheimer’s Disease, an integrated multi-omic analysis was carried out which showed a role for vitamin B2, B5, and B6 as potential therapeutic agents in the disease.

Dengue
Integrated clinical and metabolomics analysis showed an association of molecular signature with different phases of dengue infection. These molecular signatures correspond to host and parasite-related responses.

Cardiovascular Disease
Cardiovascular diseases (CVDs), including coronary artery disease, heart failure, and stroke, are global leading causes of morbidity and mortality. Conditions like hypertension, hyperlipidemia, and lifestyle factors contribute to these diseases. Major adverse Cardiovascular Events (MACE), and serious outcomes from CVDs, are key measures in clinical trials for evaluating treatment efficacy. Notably, disparities exist in cardiovascular health between rural and urban populations. Rural communities face higher CVDs and MACE burdens due to limited healthcare access, prevalent risk factors, and unique socio-economic challenges. This necessitates targeted research and interventions. Metabolomics, the study of small molecules in biological fluids, provides insights into CVD diagnosis, treatment, and prevention, offering novel avenues for targeted research. In this regard, plasma samples from myocardial infarction patients at Sri Sathya Sai Institute of Higher Medical Sciences, Prashantigram, are being analyzed using a metabolomic approach to identify potential signature profiles.

Retrospective Study of Percutaneous Transluminal Coronary Angioplasty (PTCA)
Percutaneous transluminal coronary angioplasty (PTCA), a procedure to open blocked coronary arteries, has grown exponentially since its introduction in 1977. Despite advances, restenosis, the re-narrowing of stented segments, is a common issue, often resulting in further procedures. A retrospective study is being conducted in collaboration with Sri Sathya Sai Institute of Higher Medical Sciences, Whitefield Bengaluru, to understand short- and long-term outcomes of PTCA patients by analyzing risk factors and lab parameters. Objectives include examining mortality and restenosis about various factors such as LVEF and serum creatinine levels at admission or high sugar levels. The study also explores whether gender influences late admission and whether blood pressure reduces after PTCA.

Diabetes vascular complications
Type 2 Diabetes Mellitus is a chronic and complex metabolic disorder, characterized by hyperglycemia accompanied by impaired insulin secretion and function. Chronic hyperglycemia, along with its associated abnormalities such as inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end-products (AGEs), and lipotoxicity, are the primary cause for cardiovascular diseases in T2DM. Present study intends to understand the relationship of multiple factors associated with pathophysiology of cardiovascular disease by integrating multi-omic, clinical and in vitro model systems.

FUNGI IN HEALTH AND ENVIRONMENT

Exploring Bioactive Compounds of Endophytic Fungi Associated with Swietenia Macrophylla and Bauhinia purpurea
Endophytic fungi identified as Alternaria alternata BRN 05 and Nigrospora sphaerica BRN 01 were cultivated in two different media – full-strength (FS) and quarter-strength potato dextrose broth (QS). We conducted a comprehensive metabolic profiling of the crude extract using LC-MS-QTOF, both in positive and negative modes. Targeted analysis of the extract was performed using a library of approximately 850 metabolites, with each molecule’s conformation determined through fragmentation analysis. The metabolites were classified based on their occurrence in the respective media. Unique metabolites were found exclusively in the QS media, while others were common to both FS and QS. For untargeted analysis, we utilized GNPS and Classical molecular networking, and the resulting data were analyzed using the Cytoscape software.
Furthermore, we conducted in-silico studies employing ensemble docking and molecular dynamics simulation to understand the interactions between the identified compounds and alpha-glucosidase. To assess cytotoxicity, we performed cell viability assays using normal cell lines.

Microbes in Waste Water
Our focus is on identifying potential fungal isolates collected from domestic wastewater treatment plants for exploring their bioremediation properties and their effectiveness in the biomedical field. Three Aspergillus isolates which are molecularly identified, showed prominent results concerning remediation of dyes and biomedical activities. Aspergillus tamarii has shown good biosorption ability on two commercially used textile dyes Malachite Green and Reactive Black 5, both being carcinogenic to living beings and affecting the environment adversely. A. tamarii decolorized 95% of the said dyes up to 100 mg L⁻¹ concentration. Treated samples were further investigated based on the spectroscopic and chromatography methods for any toxic by-products, which was then tested against living specimen (bacterial strains from wastewater). It showed no adverse effect on them and the fungal biomass could be regrown after taking up the dyes.

Fungal Biotechnology: Potential Applications of Fungi for Micro-pollutant Degradation
Organic micropollutants are persistent and occur in the environment in concentrations ranging from a few ng/L to several ug/L. The widespread presence of micropollutants in the environment has become a major cause of concern. The focus of our research is to harness the potential of locally isolated fungi for organic micro-pollutants remediation. In this regard we have isolated fungi from wastewater and soil namely MDWWF-2,5,6 and 8, and two novel strains of Aspergillus arcoverdensis and Aspergillus melleus which have shown the potential against selected micropollutants (Triclosan, malathion, methoxychlor, diclofenac, ciprofloxacin, etc.). Currently, we are working on finding out the best and most economical mechanism to counteract the pollutants, which includes intra-extra cellular enzymes and later the applications to treat the contaminated water.

Wastewater Analysis, Treatment, and Energy Recovery
Treated wastewater has assumed a lot of significance in water-stressed regions. There is a need to devise low-cost, low-maintenance approaches towards the treatment of domestic wastewater so that it can be disinfected and reused for secondary, non-potable applications. The WATER laboratory in the Department of Biosciences focuses on problems associated with the development of affordable methods for wastewater analysis, treatment, and energy recovery. The work presently underway involves the optimization of operational parameters for the treatment of domestic sewage in the STP located in Prasanthi Nilayam using plant-based coagulants.

Protein Structure and Function
Protein Structure and Function laboratory focuses on understanding the structural and functional dynamics of proteins using in vitro and in silico experimental methods. Making use of the fundamental knowledge obtained, we also explore using the proteins for various biotechnological applications. Specifically, we focus on revealing the moonlighting enzyme function of oxygen carrier proteins – Hemocyanins and apply the biomacromolecules in the fabrication of enzyme-based biosensors. Further, we also carry out Computer Aided Drug Design and Discovery, targeting proteins involved in infectious and non-infectious human diseases. Our efforts involve virtual screening with natural product libraries by molecular docking followed by molecular dynamics simulations.