Research

Billions of people are affected by fungal pathogens worldwide, including the recent mucormycosis outbreak in India. WHO has recently recognized and highlighted the fungal burden in the population and the need for directed research. Unfortunately, the current antifungal armamentarium is inadequate, and the development of new drugs takes decades. Other potential strategies being explored include combination therapy and drug repurposing, which are limited by the emergence of drug resistance. Studies have shown the widespread drug resistance in the pathogens, while multi-drug resistance is emerging as a nightmare. Thus it becomes crucial to understand the resistance evolvability in the context of repurposed drugs and drug combinations. This proposal includes phenotyping, evolving, and analysing 1000 strains of S. cerevisiae, the fungal model of drug resistance. The results of this study will elucidate the correlation of genetic factors, drug interactions, and resistance evolvability, which will help in better therapeutic paradigms for patients.

Keywords: Antifungals, repurposed drugs, drug interactions

Supervisor: Dr. Himanshu Sinha, Systems Genetics Lab, IIT Madras, India

In the case of cancer, macrophages alone can contribute to nearly half of the immune cells located in the tumor microenvironment (TME). Owing to this aspect, the macrophages in TME are being researched in various fields with countless approaches to enhance their anti-tumor nature. In recent times, a new field of approach called Immunometabolism has gained significance. It is the study of targeting the metabolic pathways of the immune cells and altering their physiological and functional properties to our needs. It has been demonstrated that the Tumor Associated Macrophages (TAMs) which are found abundantly in TME is polarized to an immunosuppressive M2 state creating an environment favorable to promote tumor cells and affecting various immunotherapy efficacies negatively. This polarization of TAMs are induced by various factors found in TME secreted by tumor cells. The repolarization of TAMs can be linked to various signaling and metabolic pathways. One of the most significant signaling pathways is one which is initiated by macrophage colony-stimulating factor (MCSF) released by tumor cells in the TME that binds to colony-stimulating factor 1 receptor (CSF1-R) on TAMs and promotes the repolarization to M2 phenotype through the downstream signaling pathways. It has to be noted that M1 and M2 macrophages are not only different in their phenotypical and functional profile but there are significant differences in their metabolic profile as well. For instance, M1 phenotypes favor energy production through glycolysis, but in the case of M2 macrophages, fatty acid oxidation (FAO) is the preferred method of energy generation. Here, this works tries to demonstrate the synergistic effect of a CSF1R inhibitor, BLZ945, and Etomoxir (ETO), a small molecule inhibitor of FAO that targets the carnitine palmitoyl transferase-1 (CPT-1). It was hypothesized that CSF1R inhibitor would inhibit one of the vital signals that induced the polarization of the M2 state, and ETO can prevent the metabolic profile changes which lead to the phenotypical and functional changes. Both of the inhibitor molecules were coupled with cholesterol and are delivered to the macrophages in the form of liposomes, which are produced by the standard lipid hydration procedure.

Keywords: Metabolic Reprogramming, Tumor Associated Macrophages (TAMs), Cancer Immunotherapy, Immunometabolism, Etomoxir (ETO), BLZ945.

Supervisor: Dr. Ashish Kulkarni, Immunoengineering Lab, UMass, Amherst, MA, USA

Project: Undergraduate Dissertation Project

Clinically, urea detection in the blood serum becomes important for renal and hepatic dysfunction. So far, its conventional detection has been limited by difficulties due to the requirement of extensive pretreatment of samples, longer processing time, and so on. In this context, electrochemical biosensors can serve as an effective alternative for sensing analytes present in trace amounts. The advent of nanotechnology has boosted the electrochemical sensor field because the nanoparticles show increased applicability to fabricate the sensor with increased conductivity. Incorporation of urease enzyme into the nanoparticles can make the sensor to be more specific and sensitive. For the effective use of enzyme in the sensor, it becomes essential to immobilize the enzyme on the surface of the electrode and improve its conducting properties for increasing sensitivity and stabilizing results. Here we introduce engineered Prussian blue nanocubes inlaid with gold nanospheres and chitosan as a matrix to fabricate the electrode that ensures effective immobilization of the urease enzyme, which in turn facilitates sensitive detection of urea, ensuring specificity. The gold-prussian blue nano interface serves to augment electron transfer at the electrode surface enabling rapid response and improved sensitivity. The work focuses on the characterization of the engineered nanoparticles using UV-Visible spectroscopy, SEM, and  TEM and the detecting property of the sensor by Cyclic Voltammometric studies. The lowest limit of detection was found to be 40µM.

Keywords: Urea, Prussian blue Nanoparticles, Gold Nanoparticles, Electrochemical sensors, Urease

DoI: https://doi.org/10.1007/s11696-023-02775-7 

Supervisor: Dr. Uma Maheswari K, Electrophysiology Lab,  SASTRA Deemed to be University, India

Project: Undergraduate Research Project