Investigating the mechanism of Parkinson’s disease pathogenesis in test tube
Parkinson’s disease (PD) is a common neurological disorder prevalent mostly in elderly people. This is characterised by progressive loss of brain cells/neurons in specific regions (substantia nigra) of the brain resulting in gradual decline in the sufferer’s motor skills. Mutations in protein, α-synuclein is associated with rare early onset familial forms of PD. The presence of abnormal clumps (aggregates) of the same protein in the neurons surviving in affected regions of PD patients’ brains indicate the key role of α-synuclein in the pathogenesis of PD.
Identifying the mechanisms of origin and backward propagation of oto-acoustic emissions
Deafness is the most prevalent sensory disability across nations. Unlike other senses, hearing has been least understood owing to the challenge in accessing the deeply positioned inner ear. The long term goal of our Auditory Biomechanics Lab at IIT Bombay is to develop a better understanding and effective diagnosis of hearing loss by investigating active vibroacoustics in the inner ear using novel instrumentation as well as computational modeling.
Radiant UV sunscreens for young and shiny skin
Sunscreen products work by absorbing or scattering UV radiation. Formulating superior sunscreen is of utmost importance in protecting our skin from sunburn, skin cancer and other deleterious effects. This is especially true for people with light skin due to lower concentration of melanin in their skin, which is the natural absorber and dissipater of UV radiation. The normal zinc oxide (ZnO) used as an active ingredient in sunscreen are micro-dimensional and because of this, they scatter light and appear white when applied on the skin, which is not aesthetically pleasing.
Disease diagnosis: Chemical species detection in body fluids
Among the several essential trace elements of biology, iron, copper and zinc are three most important and crucial ones for life since two-thirds of the metalloenzymes performing various functions in the human body comprise these elements in the form of their ions, viz., Fe 2+/3+ , Cu1 +/2+ and Zn 2+ . Perhaps cobalt can be placed next to it though there are only limited number of enzymes in human body based on this element. The presence of these ions in human tissue in their optimal concentrations is essential for healthy life.
Separation of plasma from blood at the point-of-care
Separating plasma from cellular elements of blood is imperative in disease diagnostics. Conventionally, blood plasma is separated in a centrifuge. However, this process of separation is difficult to replicate at the microscale, requires large sample volume, and is laborious and time consuming.
Focusing of cells in a bio-microdevice
Hydrodynamic focusing is a simple yet effective technique for flow focusing and control. It can be utilised in applications such as on-chip microfluidic flow cytometry, flow switches, generation of microdroplets, and micromixers. Hydrodynamic focusing can be 2D or 3D.In 2D focusing, the sample fluid is compressed/ sandwiched only in one direction by the two side flowing sheath fluids. However, 3D focusing allows for sample being completely surrounded with sheath fluid in all directions, and this is realised by compressing the sample flow in both the horizontal and vertical directions.
NMR-based structural biology laboratory
The cellular processes in the human body and all other organisms are very complex and each event is intertwined with numerous other processes. There are two ways to study these processes. One can either study the cascade of events as a whole to see how they affect the functioning of the cells, or the process can be broken down into its constituting molecules and each molecule studied individually in detail. In the second approach, the properties of the molecules studied individually are then patched together to give an in-depth account of what happens in the cell.
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.