Team Immuno-metabolic reprogramming during viral infection
We aim to understand metabolic reprogramming during viral infection using multi-omics system biology and experimental assays.
Project 1: Immuno-metabolic reprogramming during viral infection
Viruses rewire host cell metabolism by altering central carbon metabolic pathways such as glycolysis, gluconeogenesis, PPP, TCA cycle, amino acid synthesis/degradation, and lipid synthesis. Increased glycolytic flux is one of the predominant changes induced by viral infection for adequate viral replication. We aim to understand metabolic reprogramming during viral infection using multi-omics system biology and experimental assays.
Viruses are obligatory parasites and entirely rely on their hosts for their replication. This reliance results in significant metabolic flux alterations in the host cells, cell-specific viral replications, and production leading to changes in host metabolism. In particular, virus infection leads to substantial metabolic alterations in glycolysis rates and changes in ATP production rates. The changes in the energy metabolism can therefore be seen as an evolving property of the combined host-virus metabolic system. It could be related to changes in host cellular demands arising from viral production. Regardless of its cause, the entanglement between host metabolism and viral production opens the possibility to perturb the host-metabolism as a way of limiting viral production.
We combine machine learning and data integration techniques with biological network analysis and genome-scale metabolic modeling to characterize the metabolic and signaling rearrangement of host cells upon viral infection and identify potentially targetable genes and pathways using in vitro assays.
Currently, we are working with Human Immunodeficiency viruses (HIV), Crimean–Congo hemorrhagic fever viruses (CCHFV), Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), and dengue viruses (DENV) and in the process of extending to other RNA viruses. In the lab, we used methods like single-cell metabolomics by flow cytometry, RNAscopeTM, RNAflowTM, FlowCytometry, immunohistochemistry, and other conventional molecular and cell biology methods.
Project 2: Immune-metabolism and aging
We are interested in understanding the dysregulated immune-metabolic profile in HIV-infected individuals on long-term therapy for clinical intervention so that we can provide a better quality of life.
With the introduction of combination antiretroviral treatment (cART), people living with HIV (PLWH) have experienced a dramatic increase in life expectancy, with a concomitant decline in AIDS-defining morbidity and mortality. A simultaneous rise in non-AIDS-associated comorbidities has been described, with a particular increment in cardiometabolic diseases, which is now one of the leading causes of death in well-treated PLWH. Our group aims to understand the genetic, cellular, and molecular mechanisms of immune-aging in PLWH on successful long-term treatment. We are applying high-throughput multi-omics technologies (e.g., epigenomics, transcriptomics, proteomics, and metabolomics), along with in vitro and ex vivo experimental methods that help bridge the gap between genotype and phenotype and to understand how it regulates immune-aging and age-related diseases in PLWH. Our studies can, therefore, provide possibilities to therapeutically target the immune-aging process through clinical or metabolic interference, to provide healthy aging in the PLWH. We are using well-defined clinical cohorts from Denmark (COCOMO), India, and Cameroon. Apart from that, we have established an aging cohort of PLWH in Sweden called AROGYA.
We have initiated an interdisciplinary study, called AROGYA which means wellbeing in Sanskrit.
The overall aims of the AROGYA project are to use complimentary inter-disciplinary expertise to unravel the physiological and molecular pathways that underline the premature aging of the immune system (immune-aging) and to potentially generate novel therapeutic approaches for age-related diseases with a focus on the people who are living with HIV (PLHIV).
The study is funded by the Swedish Research Council interdisciplinary grant.
To know more - visit: https://arogya.ki.se/.