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Industrial Research And Consultancy Centre

Where does protein synthesis begin in P. falciparum?Too many choices!

Human malaria is caused by parasites (Plasmodium falciparum and Plasmodium vivax) that are introduced into the body by the bite of a female Anopheles mosquito. These parasites first invade the liver and then the red blood cells (Fig. 1). In both the liver and red blood cells, parasites multiply so rapidly that one infected person can have as many as several billion parasites in his/her blood cells. To carry out this massive multiplication, parasites need to copy themselves.

Solving the sugar binding puzzle

Periplasmic substrate binding proteins (SBPs) bind to a specific ligand with high affinity and mediate their transport into the cytoplasm via the cognate inner membrane ATP binding cassette (ABC) proteins. Because of very low sequence identities, understanding the structural basis of substrate recognition by SBPs has remained very challenging. A peri plasmic glucose binding protein from Pseudomonas putida CSV86 (ppGBP) is found to be highly specific towards glucose with an affinity of ~0.3 μM and has very low specificity towards galactose.

Cell and its surroundings: A tug-of-war that determines cell fate

Our health depends on health of the cells that constitute our body. The trillions of cells in our body must function properly and synchronously day in and day out to keep us healthy. As a result, it is very important to identify and understand the role of different factors that keeps cells happy. One of such important factors is the tissue micro-environment. Just like us, different cells function best in different environments. That’s why micro-environment of brain is different from liver.

Mechanism of genome segregation and epigenetics

Our group works to understand the molecular mechanism of segregation of chromosomes and the extra-chromosomes during cell division using well known eukaryotic fungal model, Saccharomyces cerevisae and the most prevalent fungal pathogen, Candida albicans. We also work on epigenetics mechanism to understand how genome stability and morphogenesis in C. albicans can be influenced by this.Faithful chromosome segregation is the key to maintain genome stability.

Engineering immune cells via 3D matrices for cancer immunotherapy

Cell-­based cancer immunotherapy involves modification of immune cells ex vivo and subsequent infusion; this is referred as adoptive cell transfer (ACT) therapy. However, poor survival and persistence of infused immune cells limit its efficacy treatment. Our lab with has expertise in developing 3D hydrogel systems and is trying to utilise these hydrogels for in vivo gene delivery, thereby, overcoming problems pertaining to ACT.Gene delivery vectors can be encapsulated in a 3D hydrogel and released in a sustained and localised manner leading to programming of desired cells in situ.

Semi-synthetic hydrogel matrices for studying differences in cell behaviour in 2D and 3D micro-environment

Cells in vivo are arranged in a complex micro-environment consisting mainly of extracellular matrix (ECM) and soluble factors. Researchers have tried to replicate the ECM by utilising artificially engineered matrices to provide support for cell growth. Our group has developed semi-­synthetic matrices consists of polyethylene glycol diacrylate and gelatin methacrylate which will be used to study how cells respond to different micro-­environment.

Understanding why vitiligo develops in human skin and finding the effective, affordable and long-lasting treatment

Vitiligo is a depigmentation disorder in which white patches appear on skin due to selective damage of melanin producing cells of the skin called melanocytes. Destruction of melanocytes causes hypo-pigmentation of the hair, skin and other mucosal surfaces. Depending on the geographical location within India, the prevalence of vitiligo ranges from 0.09% to 8%, with an average age of onset of symptoms at about 20 years, its occurrence appears to be equal between both genders and its rate of occurrence doesn’t vary according to skin type or race.

Technology development for gene therapy with CAR-T cells:The most effective cancer treatment

Chimeric Antigen Receptor-T cell therapy (CAR-T cell therapy) has demonstrated remarkable success in long-term remission of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Very recently, FDA approved the anti-CD19-CAR-T cells developed by Novartis for the treatment of B-ALL. However, this technology has not yet been designed and developed in India. Considering socioeconomic conditions of patients in our country, recently developed CAR-T-cell therapy will be unaffordable to majority of our patients.

Cancer stem cells: The seeds of cancer and their roles in cancer progression

Cancer stem like cells are a heterogeneous population that have been identified in several cancers. They are considered to be the seeds through which cancer progresses and survives in the body. Since these cells are very different from the bulk population in the tumour, they also show differential behavior towards various treatment options.

Biophysics of cancer

High mortality in cancer is attributed to cancer metastasis–the multi-stage process which includes invasion of tumor cells through the basement membrane, entry into blood vasculature, entry into secondary organ and its colonisation. Understanding mechanisms of cancer invasion represents one of the major research directions of our group. For this we combine traditional cell and molecular biology with biophysics and computational biology. We are currently working on the following aspects:

Tissue adhesives

In clinical practice, sutures, staples and clips are widely used as conventional wound closure devices. These devices have to be administered invasively, thus leading to discomfort to the patients also poses increase risk of microbial infestation at the wound site and take a long time to repair. To minimise and/ or eliminate the high chances of infection and transmission of blood-borne diseases associated with suturing, tissue adhesives have garnered importance in tissue repair as sealants.

Induction of embryonic stem cell differentiation by physical cues

Mouse embryonic stem cells (mESCs) are pluripotent stem cells capable of differentiating into many cell types based on the growth factors and physical cues provided by the micro- environment. These biophysical cues of the substrate are found to regulate cellular processes ranging from cell division to cell differentiation. Subtle changes in bio-chemical or physical parameters of the micro-environment are found to trigger lineage specific differentiation.

Microtubule targeted anti-tubulin agents for cancer

Microtubules are filaments formed by the polymerisation of tubulin proteins. Microtubules play a crucial role in many important cellular processes such as maintaining cell shape, intracellular transport, cell motility and cell division. During cell division, genetic material is divided into two daughter cells with the help of microtubules. Cancer begins as over proliferation/uncontrolled division of cells.

Molecular motor proteins-vehicles of cellular transportation system

Cell is the basic unit of life and can be often compared to a city. Cities have power plants, cells have mitochondria. Cities have factories, cells have ribozymes and endoplasmic reticulum. Cities have depots and ware houses while cells have Golgi bodies. One of the most important aspects of the city without which it cannot sustain its operation is the transportation system i.e. roads, rails, trains and vehicles. Cells have a transportation system whereby microtubules and actin filaments form a network of roads.

Crossing barriers: Uncovering the smart tactics to sneak into the host

The human body is bordered by several cellular barriers that define the frontier between the internal milieu and the external non-sterile environment. In addition to their physiological roles, these host barriers provide both physical and immune defense against microbial infection. Yet, many pathogens have evolved elaborate strategies to target these lines of defense, resulting in disruption of barrier integrity and dissemination into deeper tissues.

Developing fungal cells as factories

Molecular enzymology and fungal metabolic regulation form the core strengths of our research. An emerging approach to understand and exploit metabolic processes is metabolic / pathway engineering. This implies a targeted and purposeful manipulation of the capabilities of an organism. Our group is pursuing this broad research objective with the acidogenic metabolism of Aspergillus niger (A.

Non-genetic heterogeneity in Saccharomyces cerevisiae:A rule rather than an exception

Micro-organisms have evolved an impressive array of gene regulatory mechanisms to adapt to the constantly changing environmental conditions. However, even the exquisite gene regulatory mechanisms cannot escape from the cul-de-sac of physical constraints, leading to stochastic or ‘noisy’ gene expression. Interestingly, instead of evolving mechanisms to subdue the noise and lead a detenninistic life style, micro-organisms seem to have evolved mechanisms to use this noise to their advantage.

A versatile and evolving Pseudomonas sp. microbial degradation of carbaryl: Evolution and application

Carbaryl is widely used as a pesticide in the agricultural field since 1958. Apart from the desired effects, the toxicity of carbaryl to beneficial organisms like bees, earthworm and marine fishes is a cause of concern. Its extensive usage has led to environmental pollution. Within a decade of carbaryl application in the agricultural field,many microorganisms with ability to degrade it were isolated. Pseudomonas sp. isolated from soil in our lab converts carbaryl into cell biomass via.

Preferential utilisation of aromatics over glucose by Pseudomonas: An asset to bioremediation

Aromatic compounds are most extensively used in various industries like plastic, paint, pesticide, petrochemical etc. These compounds are released into the environment due to various natural and anthropogenic activities leading to pollution. Biodegradation is a viable way to remove these pollutants to harmless metabolites. Multiple factors play an important role in efficient Multiple factors play an important role in efficient bioremediation of pollutants by microorganisms viz.

Breathe easy: Biomimetic lung surfactants for critical care respiratory diseases

Acute critical care lung diseases like Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury have a high mortality rate worldwide and especially in developing countries like India. Several diseases can lead to critical lung conditions of ARDS like malaria, leptospirosis, and undiagnosed fever followed by pneumonia, urinary tract infections, and pancreatitis. Mechanical ventilation currently used for therapy in ARDS by itself harms the lungs. At present, one of third of ARDS patients succumb to the condition within the first couple of days of intensive care.