The NMIMS Sunandan Divatia School of Science is strongly driven by highly qualified scientific talent pool. The main focus of our R & D activities has been to conduct applied research at the interface of Chemistry and the Biosciences on current problems of national importance.
Various research oriented projects in the area of Biological Sciences and Chemical Sciences that have been initiated at Sunandan Divatia School of Science have been highlighted below:
The work in this area at the School involves use of adult, embryonic and pluripotent stem cells to understand fundamental mechanism of pluripotency and differentiation. Previously at the School extensive work was carried out on human umbilical cord derived mesenchymal stem cells (hUC-MSCs), their differentiation into hepatocytes and also assessing the use of nanoparticles for in vivo tracking of hUC-MSCs. The research on human pluripotent stem cells are focused on understanding the role of histone modifiers during differentiation into pancreatic and neuronal cell lineages. Differentiation of pluripotent stem cells requires precise orchestration between changes in chromatin, transcription, translation, metabolism and cell morphology. Pluripotent stem cells have an “open chromatin” and hence they can differentiate into all three germ lineages such as endoderm, mesoderm and ectoderm in response to extraneous signals. Chromatin remodelling is an essential step towards differentiation in the case of pluripotent stem cells. Two most widely studied chromatin modifications in stem cells are DNA methylation and histone modifications. Polycomb group (PcG) proteins are developmentally crucial set of histone modifying proteins that bring about gene repression. PcG form multiprotein complexes called Polycomb Repressive Complexes (PRC) such as PRC1 and PRC2.
We aim to study the PcG expression, location as well as histone modifications catalysed by them at developmentally crucial genes during pancreatic and neuronal differentiation from human ES and iPS cells. At the School of Science, the following projects have been undertaken to understand the role of Polycomb Group (PcG) proteins during human pluripotent stem cells differentiation:
We have received funds from Department of Science and Technology (DST) under the Early Career Research Award (ECR) scheme for one of the above mentioned projects.
Oral cancer ranks as number one cancer in males and fifth most common cancer in females in India. Besides the survival rate has not changed in the past four decades, due to a majority of patients diagnosed in the advanced stages of cancer. The high incidence of oral cancer in India is due to the prevalence of exposure of our population to the risk factors of tobacco- chewing and smoking, alcohol consumption, areca nut chewing and Human Papilloma virus types HR-HPV16/18. Microbiome analysis may be useful as indicators for detection of high risk precancerous states, cancer stage association and response to treatment as well as post-treatment monitoring. Microbiome analysis in cancer and non-cancer population from American and European countries and its link with cancer have been reported. Profiling and analysis of microbiome will generate population specific database and indicate their association with cancer, which can help in assessing and controlling the complications in cancer therapies.
Telomeres are the ends of linear chromosomes and function as safeguards of the genome. Telomeres shorten upon each cell division due to unidirectional nature of DNA polymerase leading to critically short telomeres which may lead to loss of critical genes located in proximity to the telomeres. To ensure faithful genome replication and overcome telomere attrition cells express a special enzyme called telomerase which can replicate telomeres. While most somatic cells lack telomerase and thus have limited lifespan, stem cells, immune cells, germ cells and 80 % of cancer cells express telomerase making them replicatively immortal. Telomeres also encounter end protection problem which arises due to recognition of linear chromosome ends as double strand breaks that may be recognized by DNA damage machinery and result in apoptosis or senescence. To overcome this, human telomeres are protected by a specialized six subunit complex called as shelterin complex. Telomerase and shelterin along with several other telomere associated proteins function as safeguards for the genome and deregulation of any of these components results in telomere dysfunction and diseases like accelerated aging or cancer.
Investigating the role of telomere associated proteins in cancer and aging.
With the advent of nanotechnology, new materials are being explored for their application in biomedical arena. Nanoparticle mediated drug delivery has helped us to achieve high payload and specificity of chemotherapeutics thereby reducing their adverse effects on patients. The nanomaterials are also very useful for fabricating biosensors for detection of specific diseases. Department of Chemistry at Sunandan Divatia School of Science is involved in Nanoresearch with an objective to synthesize various nanomaterials for multimodal applications. One of them being, synthesis of dendrimer based nanoparticles for early detection of liver diseases. While on other hand, we are also working towards development of biocompatible magnetic nanoparticles for imaging, targeting and in-vivo tracking of stem cell. Yet another approach of our research is concomitant to the saying "There is plenty of room at the bottom" by Richard Feynman-Nobel Laureate. With an understanding that nanomedicine can offer plenteous ways of treating cancer, we ought to design a multimodal nano-platform for dual drug therapy and multiple treatment modalities (photo-thermal, Chemotherapy, magnetic hyperthermia).
Besides biomedical applications, we are also involved in designing advanced nanomaterials for their use in alternative energy generation and storage such as fabrication of supercapacitors. With several collaborations abroad, our department is involved in multi-disciplinary research with an aim to develop functional nanomaterials for a rich variety of applications.
Use of arsenic and its derivatives dates back to more than 2400 years with Arsenic trioxide (As2O3) being successfully implemented to treat refractory or relapsed Acute Promyelocytic Leukemia (APL). One of its limiting factor for cancer treatment include its toxicity against normal cells. Nanoparticles offer the flexibility with sustained-release characteristics, ability of surface-modification, bio-ligand attachment thereby offering a plethora of options. Hence, we attempted to synthesize biocompatible As2O3 nanoparticles (NPS) that would provide lowered toxicity and high anti-cancer activity for various solid tumors. In vitro anticancer efficacy of biopolymer coated As2O3 NPs was investigated in LNCaP and PC-3 cell lines, by assessing DNA damage, changes in epigenetic modulations, expression level of apoptotic markers and cell cycle analysis following treatment with As2O3 NPs. Our results demonstrated that the nanoparticulate formulation of dimercaptosuccinic acid (DMSA) and chitosan coated As2O3 is capable of inducing morphological changes, DNA damage and caspase-dependent apoptosis along with the expression of cyclin-dependent kinase inhibitor p21 by upregulation of Bax and downregulation of Bcl-2 and Bcl-xL proteins. . We plan to explore and have a detailed understanding of the molecular interaction between the drug i.e arsenic trioxide with the coating material using molecular modelling in silico. Blood compatibility studies would be done to understand the effect of the drug on body fluid specifically blood cells. Hence, this would help us in gaining a deep understanding of the interaction of arsenic trioxide nanoparticles on cancer cell lines.
Significant efforts have been made in the field of nanotechnology to develop biocompatible nano-size carriers that can achieve better drug loading efficiency, storage stability, and targeted delivery. Encapsulating drugs into these carriers can not only increase the solubility of some drugs but it can also protect the human body from the harmful effects of some of the drugs as also protect the drugs from being degraded in the circulation, therefore, increasing the bioavailability and the therapeutic outcome. The use of nano-carriers can further increase the specificity of the drugs while reducing the associated side effects.
In terms of delivering multiple drugs for combination therapies, nanoparticle-assisted combination therapy allows rational optimization of the drug dosage by unifying the pharmacokinetics and biodistribution pattern of different drug molecules. Despite the advances in designing such multiple therapeutic systems, the major challenge in a nanoparticle-based combinatorial approach is to maintain the ratios of different types of drugs, batch-to-batch homogeneity during mass production, and avoid unwanted drug–drug or drug–excipient interactions. At the School, carriers such as niosomes, solid lipid nanoparticles (SLN), nanoemulsions and nanostructured lipid carriers (NLC) are being studied for delivery of multiple drugs used in treatment of various diseases such as malaria, rheumatoid arthritis and psoriasis through various routes of administration.
Global warming is a direct consequence of greenhouse gases emission, 72% due to carbon dioxide (CO2) emissions derived from burning of fossil fuels and leading to increasingly varying rainfall patterns, rising sea level and extreme flood situations. This heavy reliance on fossil fuels for energy results in 30.4 Gt of CO2 emission into the atmosphere.  Moreover, there is an ever increasing global energy demand from fossil fuels as a result of industrial development and population growth, particularly in developing countries. Therefore, the use of fossil fuels for energy and related emissions of CO2 are inevitable until we develop wider deployment of sustainable energy sources. Solar fuels and hydrogen energy are big hopes for this global distress. Photocatalysis using inexpensive, nontoxic and visible light absorbing materials is a potentially feasible way to make use of abundant solar energy for 2 major reactions; (1) photocatalytic water splitting to produce H2 and (2) photocatalytic conversion of CO2 into solar fuels, such as methane (CH4) and methanol (CH3OH). This is a very promising strategy to not only reduce the greenhouse gas emission but also to address the energy demands.
Recently, we have developed novel mesoporous carbon nitride (MCN-8) with C3N5 stoichiometry via nanocasting approach. MCN-8 has 3D porous and graphitic structure with both tri-s-triazine framework that is similar to that of graphic C3N4 but its surface is attached with triazole units. This unique chemical structure of MCN-8 offers a band gap of ca 2.2 eV which is significantly smaller than the graphitic carbon nitride (ca 2.7 eV). This result is quite significant as it helps MCN-8 to achieve extended absorption in visible region and higher rate of H2 evolution (Figure 1A) as compared with traditional melamine derived g-C3N4. Further research is underway to improve the charge transport and thereby to enhance the efficiency.
However, when we compare with H2O, CO2 is one of the most stable and chemically inert molecules with a linear geometry. Therefore, breaking of C=O bonds and the bending of the linear molecular structure need a large input of energy and appropriate catalysts, as compared with water splitting. Solid nanoporous materials with high surface area, large pore volume, thermal stability and inbuilt basic sites (NH2 groups) on the surface can be a perfect candidate for CO2 capture. It is expected that introduction of porosity will improve the capture of more photons due to light scattering effect inside the pores and shortening of the path length for the photo-generated charge carriers to the surface of the photocatalyst due to thin walls. Accordingly, the aim of this project is the development of multifunctional, low cost and highly basic mesoporous carbon nitrides and mesoporous Cu doped TiO2 materials for CO2 capture and its conversion to hydrocarbons by using solar energy (as shown schematically in Figure 1B).
Figure (1): (A) Time course of photocatalytic H2 evolution for MCN-8 under visible light irradiation (λ > 420 nm).  (B) Schematic diagram showing photocatalytic CO2 conversion to value added products (for ex., CH4, CH3OH is shown) by using MCN material.