Ongoing Projects
We are working with a wide range of model systems like prokaryotes such as bacteria and eukaryotes like Dictyostelium discoideum (cellular slime mould), macrophages, cancer cells, etc., to achieve a long-term goal of 1) understanding and diagnosis of infectious diseases by developing a microfluidic-based device, 2) cell-cell and cell-substrate adhesion during chemotaxis and migration. We also look into the 3) understanding of the dynamics of biofilm formation exploiting cellular motility.
01
Lab-on-a-chip device to detect Urinary tract infection and sepsis
Urinary Tract infections (UTIs) are among the most common infections, affecting over half of the population at least once in their lifetime and accounting for significant morbidity and health-care expenditure. Urine culture with antibiotic susceptibility testing takes two to three days. The widespread use of antimicrobial agents has led to the growth of multidrug-resistant pathogens, limiting treatment choices and raising expenses. Antimicrobial resistance (AMR) is emerging as a global health threat, and because of this, even common infections are becoming harder to treat with empirical antibiotics. The major driving force for the occurrence of AMR is the unregulated use of antibiotics in the outpatient clinic. Antimicrobial susceptibility testing (AST) ensures the current choice of antibiotics for treating specific infections. Despite tremendous progress in the diagnostic field, traditional culture-based AST techniques continue to be followed in routine clinical practices. This system involves several cultivation rounds and suffers long turn-around times (>48 hrs). Therefore, there is an urgent need for the development of a rapid and accurate point-of-need AST kit, which enables the evidence-based prescription of antibiotics and better tackles the ongoing rise of antimicrobial resistance. Microfluidics and microdevices are explored with electrochemical impedance spectroscopy (EIS) as an emerging AST technique because the detection process is sensitive and rapid with small sample volumes.
The flow diagram of the impedance-based lab-on-a-chip device.
02
The interplay of cell-cell and cell-substrate adhesion in eukaryotic chemotaxis
Cells work together and make group decisions in systems ranging from bacterial biofilms to wound healing, neuronal networks, and cancer metastasis.
Chemotaxis of Dictyostelium discoideum: Chemotaxis, the guided motion of cells by chemical gradients, plays a crucial role in many biological processes. In the social amoeba Dictyostelium discoideum, chemotaxis is critical for forming cell aggregates during starvation. The cells in these aggregates generate a pulse of the chemoattractant, cyclic adenosine 3’,5’-monophosphate (cAMP), every 6 min to 10 min, resulting in surrounding cells moving toward the aggregate. Dictyostelium is a fantastic model system for studying cellular collective behaviour as signalling starts with the single cells and observes an entire collective and its signalling responses and behaviours simultaneously. We are trying to understand the cellular dynamics during this collective behaviour. (Video)
Neutrophil migration: Neutrophils are innate immune cells that use directed migration to sites of injury and infection. We use Neutrophil-Like HL-60 Cells for the Study of Directed Cell Migration. We are trying to understand the interaction between bacteria and neutrophil cells. (Video)
Cell-substrate adhesion: The cancer cell and cell matrix are highly dynamic. The interaction between the cancer cell, healthy cells, and the tumour microenvironment is essential in regulating neighbouring cell behaviour. We are trying to understand the organisational principles and how they influence cancer phenotype, metastasis, and outcome. To study these problems, we try to understand the dynamics of extracellular matrix (ECM), glycocalyx-glycans, and lectins. These are critical to constructing tissue homeostasis but are dysregulated in cancer dissemination. We also look into the motor protein dynamics to understand the cellular motility and the interaction between the ECM.
Macrophage chemotaxis: Previous studies showed that the tumour cells' communication with tumour-associated macrophages is a critical factor of tumour malignant potential development. We are trying to understand the interaction between the Circulating tumour cells (CTCs) and the macrophages. This study will focus on the interplay in the tumour microenvironment between macrophages (M2a) and breast cancer cells and fibroblasts. In particular, cell-cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumour phenotypes induced in macrophages.
03
Understanding of the dynamics of biofilm formation exploiting cellular motility
It has been seen that colonies of bacteria secrete extracellular polysaccharides (EPS) during biofilm formation. Bacteria may also auto-aggregate or co-aggregate to form biofilms in pure or mixed cultures if no solid substrate is available for their attachment. Bacterial motility and chemotaxis are virulence factors that facilitate host invasion. Biofilm formation is the interplay between the motility and the available nutrient source. It is unknown whether the cells are deriving the nutrients from the host or the bacteria of the same colony. Adhesion allows cells to stay on the surface to grow into biofilms, while motility promotes aggregation and surface encounters. We are trying to understand the role of motility in biofilm formation in a recourse-limited environment.
04
Microfluidics
​To understand the fundamental behaviour of cell migration, especially chemotaxis, we design and develop different microfluidic devices to establish different gradient profiles. We also develop lab-on-a-chip devices for disease diagnosis.
Collaborators
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Prof. S. Pushpavanam
Chemical Engineering, IIT Madras
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Prof. Pallab Sinha Mahapatra
Mechanical Engineering, IIT Madras
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Prof. Sankha Karmakar
Chemical Engineering, IIT Madras
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Prof. Tuhin Subra Santra
Engineering Design, IIT Madras
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Institute of Child Health and Hospital for Children
Chennai
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Appollo Hospital
Chennai​