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Infectious Disease Biology

Infectious disease biology is one of the major mandate of ILS with a vision to work towards human health and welfare focusing on infectious diseases prevalent in India. This core area is being addressed by a group of scientists with varied and complementary expertise, working independently and in collaboration within the group to address key issues of pathogen biology, host-pathogen interaction & disease pathogenesis, immune regulation, inflammation & immunopathology, antibiotic resistance and drug discovery. Insight into pathogen biology, host response, disease onset and progression at molecular and cellular levels is crucial to identify potential drug-targets to enable specific drug-design and development. To address the issues on infectious disease biology in experimental as well as human models, ILS has developed strategic collaboration with neighbouring hospitals for obtaining patient samples and promote interaction with clinicians.

Scientists Working in the Field

Major activities undertaken during last 5 years

Immunity and inflammation group focusses on pathogen-mediated modulation of host immune system that determines the outcome of other infectious and metabolic diseases with emphasis on the ‘Hygiene Hypothesis’. This group is also addressing the genetic basis for the modulation of the host immune system and inflammation by malaria and other parasites.

Biofilm and antibiotic resistance group is attempting to identify the functional and regulatory genes involved in biofilm development in the Vibrio cholera and Staphylococcus spp. Biofilm is a survival strategy for bacteria to adapt to their hostile living environment and imparts resistance to antibiotics and host immune responses. Molecular insights into the bacterial biofilm development will help design therapies for the clinical treatment of biofilm infections by limiting biofilm formation and antibiotic resistance.

Molecular virology group works on Chikungunya virus (CHIKV). CHIKV causes self-limiting febrile illness which often progresses into severe chronic incapacitating polyarthralgia. CHIKV is highly prevalent in India and is a looming threat to human health worldwide as there is no vaccine and specific antiviral till date. The emphasis of this group is to understand CHIKV biology and pathogenesis to identify crucial viral and host proteins that can serve as targets to develop therapeutic interventions. This group is also exploring the cause and clinical severity related to CHIKV-Dengue co-infection.

Bacterial cell division group is characterizing the mechanism involved in bacterial cell division with the ultimate objective to discover novel antibacterial agents targeting bacterial cell division. Antibiotic resistance being a growing problem with devastating consequences on human health, there is an urgent need to discover novel antibiotics. This group is working with bacterial protein, FtsZ crucial for bacterial cell division and work is underway to design and synthesize small molecules that can inhibit FtsZ functions and lead to discovery of a new class of antibiotics.

Macromolecular crystallography group is attempting to unravel the viral proteins structure through crystallography studies and determine the structural and functional aspects of viral protein targets to enable structure-based drug design and development. Currently, the interaction of Influenza virus M1 protein and Dengue virus capsid proteins with host chromatin elements is being explored. The work will provide insight on how the viral proteins affect chromatin elements and alter nucleosomal organization in order to facilitate viral propagation.

Clinical proteomics group focusses on studying the disease-driven human proteome and post translational modifications to understand the whole biological process and variation due to diseases. This group is currently working on the clinical proteomic aspects of Chikungunya virus infection to identify differentially expressed proteins and determine their role in disease pathogenesis.

Chandipura virus biology group is focussing on understanding the biology and pathogenesis of Chandipura virus (CHPV). CHPV is endemic to India and infection leads to acute encephalitis with a high fatality rate (55.6%-75%). Not much is known about CHPV biology and pathology and currently, no therapeutics options and vaccines are available. Using yeast-two hybrid assays this group is attempting to delineate virus-host protein interactions and determine the crucial viral and host proteins that facilitate viral propagation and disease pathogenesis.

Autophagy group is trying to understand the mechanisms of autophagy regulation in connection with microbial infection. Autophagy plays significant role in cell-autonomous defense against intracellular pathogens and in cellular stress response. One study currently being pursued is on the molecular mechanisms of autophagy regulation during HIV-TB co¬infection.

Malaria parasite biology group is currently focussing on understanding the transmission biology of Plasmodium with emphasis on the molecular and biochemical aspects that are crucial for the development of sexual stages in mosquitoes and liver stages in vertebrate hosts. This group’s major goal in delineating these aspects is to design therapeutic strategies that interfere with the homeostasis of host-parasite networks and prevent malaria transmission.

Virus-host interaction group is attempting to understand the virus-host interaction and disease pathogenesis during infection with Flaviviruses like Dengue, Hepatitis C and Japanese encephalitis. Dengue is highly prevalent in India and causes mild fever to lethal haemorrhagic fever and shock syndrome. There is no effective vaccine and therapeutic strategies against Dengue. Currently, this group is exploring the significance of mitochondria-centric signaling in the pathophysiology of Dengue disease to identify therapeutic targets and develop effective interventions.