Photo credit: Jeyashri Rengaraju
A roundup of research articles published in the last month (16 July – 15 August 2022) at the institute:
From being asymptomatic to needing a ventilator and recovering or succumbing to the disease, we all witnessed how variable the severity of COVID-19 symptoms was. The causes to which are still being investigated. Rajesh Pandey’s lab investigated the role of long non-coding RNAs in regulating the immune response that can potentially influence the COVID-19 disease severity.
They identified differentially expressed lncRNAs by inter-group comparison between mild, moderate, severe, and mortality groups. Using gene set enrichment analysis the immune regulatory genes were found to be associated with these differentially expressed lncRNAs. On further analysis, the presence of transcription factor binding sites within the repeat elements were found in the lncRNAs. This seems to be one of the plausible mechanisms for regulation of the target genes of these lncRNAs and thus mediating immune function modulation.
Chattopadhyay P, Mishra P, Khare K, Yadav A, Mehta P, Saifi S, Swaminathan A, Devi P, Parveen S, Tyagi A, Jha V, Tarai B, Jha S, Budhiraja S, Narayan J, Pandey R. LncRNAs harbouring regulatory motifs within repeat elements modulate immune response towards COVID-19 disease severity and clinical outcomes. Clin Transl Med. 2022 Jul;12(7):e932. doi: 10.1002/ctm2.932. PMID: 35808807; PMCID: PMC9270577.
The role of lifestyle in causing Type-II diabetes is suggestive of the epigenetic mechanisms to be responsible. Insulin resistance which is the hallmark of Type-II diabetes disrupts the uptake of glucose by tissues; one of the major tissues getting affected being skeletal muscle. H19, an lncRNA has been shown to be affected with decreased in the skeletal muscle of Type-II diabetics and the animal models of obesity. Malabika Dutta’s lab showed that the decreased H19 levels in turn decrease the IRS1 levels via inhibiting IRS1 gene expression. This repression of IRS1 seems to be mediated via deacetylation caused by increased HDAC6 levels in the skeletal muscle in response to H19 decrease. H19 forms a potential therapeutic point of intervention for Type-II diabetes.
Kumar A, Datta M. H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes. Mol Med. 2022 Jul 16;28(1):81. doi: 10.1186/s10020-022-00507-3. PMID: 35842608; PMCID: PMC9287888.
The coordinated movement of ions that ensures the rhythmic beating of the heart is orchestrated by the various ion channels present in the heart muscle cells. Any abnormality in the functioning of these ion channels can prove fatal for an individual. These abnormalities are called channelopathies which could be caused due to several genetic factors. The prevalence and the associated genetic factors in India have not been studied extensively. Sridhar Sivasubbu and Vinod Scaria’s labs identified pathogenic variants in the genes that have been shown to be involved in causing cardiac channelopathies, using the IndiGenomes data set. The 0.9 – 1.8% prevalence rate was estimated by using this dataset of 1029 healthy individuals. The early detection of cardiac channelopathies which can be achieved from this study can save lives of a large number of individuals who are at risk of sudden cardiac arrest because of the presence of these variants.
Bajaj A, Senthivel V, Bhoyar R, Jain A, Imran M, Rophina M, Divakar MK, Jolly B, Verma A, Mishra A, Sharma D, Deepti S, Sharma G, Bansal R, Yadav R, Scaria V, Naik N, Sivasubbu S. 1029 genomes of self-declared healthy individuals from India reveal prevalent and clinically relevant cardiac ion channelopathy variants. Hum Genomics. 2022 Aug 5;16(1):30. doi: 10.1186/s40246-022-00402-2. PMID: 35932045; PMCID: PMC9354277.
Immunocompromised individuals are prone to fungal infections. The availability of huge genomics and proteomics data from various pathogens can be utilized to create vaccines – reverse vaccinology – to prevent fungal infections. S Ramachandran’s lab developed a computational tool that would help in narrowing down on the targets suitable for vaccine development for mucormycosis.
Bhargav A, Fatima F, Chaurasia P, Seth S, Ramachandran S. Computer-Aided Tools and Resources for Fungal Pathogens: An Application of Reverse Vaccinology for Mucormycosis. Monoclon Antib Immunodiagn Immunother. 2022 Aug 8. doi: 10.1089/mab.2021.0039. Epub ahead of print. PMID: 35939284.
Liver being the major site of metabolism for pharmaceutical drugs, gets affected by many of the drugs and many times the reason for failure of drugs in clinical trials is drug induced liver injury. Chetana Sachidanandan’s lab identified a small molecule – BML-257 – that was found to be protective against hepatotoxicity. Using zebrafish as a model to induce liver toxicity, via drugs having different mechanisms of action like metronidazole, isoniazid, and APAP, BML-257 was seen to promote liver regeneration. BML-257, which is an Akt (MAPK) inhibitor, was found to even work as a prophylactic factor and thus holds huge potential for acting as a hepatoprotective agent given along with drugs that are known to induce liver damage.
Jagtap U, Basu S, Lokhande L, Bharti N, Sachidanandan C. BML-257, a Small Molecule that Protects against Drug-Induced Liver Injury in Zebrafish. Chem Res Toxicol. 2022 Aug 15;35(8):1393-1399. doi: 10.1021/acs.chemrestox.2c00100. Epub 2022 Jul 7. PMID: 35796757