Post-transcriptional regulators of aging and dietary restriction

MicroRNAs (miRNAs) are a class of small RNAs that negatively regulate gene expression by base pairing to their target mRNAs. A number of human diseases including late onset neurodegenerative disorders and cancer are associated with aberrant expression of microRNAs and molecules that alter the function or abundance of miRNAs are emerging as potential therapeutic agents to treat diseases. The main focus of my laboratory is to utilize the genetically amenable fruit fly model system to characterize non-coding RNA mediated post-transcriptional networks that operate during aging and late onset diseases.

Aging is a risk factor for a number of non-communicable diseases including neurodegeneration, cardiovascular diseases and cancer. Thus, understanding how aging increases the risk of disease is needed to reduce the prevalence of late onset pathological conditions. Towards this goal, increasing evidence has implicated dietary/caloric manipulation – reduced calorie intake that does not incur malnutrition – as a simple means of counteracting age-related disease. Strikingly, this type of nutritional intervention increases lifespan in diverse species, including yeast, nematodes and fruit flies and non-human primates, indicating that the molecular mechanisms that underlie dietary restriction (DR) are evolutionarily conserved. Though, this anti-aging manipulation has been shown to direct profound changes in protein coding RNAs, its effect on noncoding RNAs levels remain largely unstudied. Our recent small RNA profiling analysis has identified conserved miRNAs that are modulated by dietary restriction. Our primary goal is to utilize genetic, molecular, proteomic and metabolomics approaches to test whether miRNAs can function as dietary restriction mimetics to enhance healthy lifespan.

• Ben Barres Spotlight Award, 2021
• Wellcome-DBT India Alliance Intermediate Fellowship 2018
• Ramalingaswami fellowship 2016-2017 (Relinquished)
• Concepts to Clinic-Project Development Team(CTC-PDT), Indiana CTSI grant (2016-2018)
• CSIR Senior Research Fellowship (1999-2001)
• Visiting Student scholarship from Institute of Cellular and Molecular Biology(IMCB), National University of Singapore (1999)
• CSIR Junior Research Fellowship (1996-1998)
• Recipient of Dr. Manasi Ram Memorial Award for best poster in the All India Cell Biology Conference XXII, Hyderabad (1999)
• GATE-96 (Graduate Aptitude Test in Engineering) Percentile: 99.75. All India Rank 9

• Haseeb Ul Arfin
  Project JRF
  
• Manish Pandey
  Project JRF
  manish.pandey@rcb.res.in

1. Manish Pandey, Geetanjali Chawla**. Purification of exosome-enriched proteins produced in a Drosophila cell line by size exclusion chromatography.STAR Protocols, Volume 3, Issue 4, 2022,101834, ISSN 2666-1667, https://doi.org/10.1016/j.xpro.2022.101834.
2. Pandey, M., Luhur, A., Sokol, N. S. & Chawla, G**. Molecular Dissection of a Conserved Cluster of miRNAs Identifies Critical Structural Determinants That Mediate Differential Processing. Frontiers in Cell and Developmental Biology 10, doi:10.3389/fcell.2022.909212 (2022).
3. Pandey M, Bansal S, Chawla G**. Evaluation of lifespan promoting effects of biofortified wheat in Drosophila melanogaster, Experimental Gerontology (2021). doi.org/10.1016/j.exger.2022.111697. Epub 2022 Jan 10. PMID: 35016996.
4. Kenneth A. Wilson, Manish Chamoli, Tyler A. Hilsabeck, Manish Pandey, Sakshi Bansal, Geetanjali Chawla**, Pankaj Kapahi**. Evaluating the beneficial effects of dietary restriction: A framework for precision-nutrigeroscience Cell Metabolism (2021), https://doi.org/10.1016/j.cmet.2021.08.018
5. Manish Pandey, Divya Ojha, Sakshi Bansal, Ambadas B. Rode**, Geetanjali Chawla**. From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases.Mol Aspects Med, doi: 10.1016/j.mam.2021.101003
6. Manish Pandey, Sakshi Bansal, Sudipta Bar, Nicholas S. Sokol, Jason M. Tennessen, Pankaj Kapahi* and Geetanjali Chawla*. miR-125-chinmo pathway regulates dietary restriction dependent enhancement of lifespan in Drosophila. eLife 2021;10:e62621 DOI: 10.7554/eLife.62621
7. Manish Pandey and Geetanjali Chawla**. Total RNA isolation from Drosophila using TRIzol based reagent. In: H. A. Ranganath and S.C. Lakhotia (eds) Experiments with Drosophila for Biology Courses. (2021) pp 341-350 Indian Academy of Science, Bengaluru, India.
8. Manish Pandey, Sakshi Bansal and Geetanjali Chawla**. Genomic DNA isolation from Drosophila. In: H. A. Ranganath and S.C. Lakhotia, (eds) Experiments with Drosophila for Biology Courses. (2021) pp 329-335. Indian Academy of Science, Bengaluru, India.
9. Simranjot Bawa, David S Brooks, Kathryn E Neville, Marla Tipping, Md Abdul Sagar, Joseph A Kollhoff, Geetanjali Chawla, Brian V Geisbrecht, Jason M Tennessen, Kevin W Eliceiri, Erika R Geisbrecht (2020) Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth Elife. 2020 March 30; 9:e52358 DOI: 10.7554/eLife.52358.
10. Yen-Chi Wu, Geetanjali Chawla and Nicholas Sokol (2020) let-7-Complex MicroRNAs Regulate Broad-Z3, Which Together with Chinmo Maintains Adult Lineage Neurons in an Immature State G3: GENES, GENOMES, GENETICS. doi.org/10.1534/g3.120.401042
11. Pandey M, Bansal S, Chawla G^**. (2019) Molecular Approaches for Analysis of Drosophila MicroRNAs In: Mishra M. (eds) Fundamental Approaches to Screen Abnormalities in Drosophila. Springer Protocols Handbooks. pp 169-188. Springer, New York, NY
12. Krejčová G, Danielová A, Nedbalová P, Kazek M, Strych L, Chawla G, Tennessen JM, Lieskovská J, Jindra M, Doležal T, Bajgar A. Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense. Elife. 2019 Oct 14;8. pii: e50414. doi: 10.7554/eLife.50414.
13. Geetanjali Chawla^** (2019). Healthy Aging research in India. Journal of Experimental research on human growth and Aging. Vol. 2, Issue 1, Aug. 28, 2019.
14. Hongde Li, Madhulika Rai, Kasun Buddika, Maria C. Sterrett, Arthur Luhur, Nader H. Mahmoudzadeh, Cole R. Julick, Rose C. Pletcher, Geetanjali Chawla, Chelsea J. Gosney, Anna K. Burton, Jonathan A. Karty, Kristi L. Montooth, Nicholas S. Sokol and Jason M. Tennessen. (2019) Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development. Development Posted Online August 9, 2019, doi:10.1242/dev.175315
15. Li H, Chawla G, Hurlburt AJ, Sterrett MC, Zaslaver O, Cox J, Karty JA, Rosebrock AP, Caudy AA, Tennessen JM. (2017) Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth. Proc Natl Acad Sci U S A. 114:1358
16. Chawla G^#, Luhur A^#, Sokol NS. (2017) Analysis of MicroRNA Function in Drosophila. Methods Mol. Bio. 1478:94.
17. Chawla G^**, Deosthale P, Childress S, Wu YC, Sokol NS^** (2016) A let-7-to-miR-125 MicroRNA Switch Regulates Neuronal Integrity and Lifespan in Drosophila. PLoS Genet. 12:e1006247
18. Chawla G^**, Sokol NS^** (2014) ADAR mediates differential expression of polycistronic microRNAs. Nucleic Acids Res. 42:5255
19. Luhur A , Chawla G^#, YC Wu^#, Li J , Sokol NS, (2014) Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proc Natl Acad Sci U S A. 111:1426
20. Luhur A^#, Chawla G^#, Sokol NS. (2013) MicroRNAs as components of systemic signaling pathways in Drosophila melanogaster. Curr Top Dev Biol. 105:123
21. Chawla G^**, Sokol NS^** (2012) Hormonal activation of let-7-C microRNAs via EcR is required for adult Drosophila melanogaster morphology and function. Development. 139:1797
22. G Chawla^**, Sokol NS^** (2012 ) MicroRNA pathways in Drosophila. From Nucleic Acids Sequences to Molecular Medicine. [Springer book]
23. Zheng S, Gray EE, Chawla G, Porse BT, O'Dell TJ, Black DL. (2012) PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci. 15:381-8
24. Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL. (2011) Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem. 286:10007-16
25. Chawla G^**, Sokol NS^** (2011) MicroRNAs in Drosophila development. Int Rev Cell Mol Biol. 286:65
26. Chawla G, Lin CH, Han A, Shiue L, Ares M Jr, Black DL. (2009) Sam68 regulates a set of alternatively spliced exons during neurogenesis. Mol Cell Biol. 29:201-13
27. Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black DL. (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21:1636-52
28. Boutz PL, Chawla G, Stoilov P, Black DL. (2007) MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 21:84
29. Chawla G, Sapra AK, Surana U, Vijayraghavan U. (2003) Dependence of pre-mRNA introns on PRP17 a non-essential splicing factor:implications for efficient progression through cell cycle transitions. Nucleic Acid Research. 31:2343.
30. Lindsey-Boltz LA^#, Chawla G^#, Srinivasan N, Vijayraghavan U, Garcia-Blanco MA. (2000) The carboxy terminal WD domain of the pre-mRNA splicing factor Prp17p is critical for function. RNA. 6:1289-305



**Co-corresponding authors
#Co-authors