Research

G. Aneeshkumar Arimbasseri

M. Sc.
Mahatma Gandhi University, Kottayam, Kerala

Ph. D.
Center for Cellular and Molecular Biology, Hyderabad

Postdoctoral Research
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD USA
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC USA 

Email
aneesh@nii.ac.in

 

Group Members

Mr. Khem Singh Negi, Ms. Anamica Das, Mr. Gagan Dev, Ms. Neha, Mr. Chen Chongtham, Mr. Somdeb Chattopadhyay

Summary of Research

Nutrients, metabolism and gene expression
A healthy life depends on the balance between nutrient uptake and the metabolism of the individual. While macronutrients serve as the source of both energy and structural building blocks of the organism, micronutrients are essential for various activities that are essential for metabolic processes including energy generation. The energy and chemical homeostasis of the body is maintained by multiple pathways and the ratio of different macronutrients in the staple diet determines which pathway is predominant in an organism at a given time. The bioavailability of the micronutrients can also differentially influence these pathways, setting stage for a complex interaction network of different nutrients and pathways, the outcome of which will determine the health of the individual. Such interactions could also be influenced by the genetic polymorphisms, possibly creating individualistic differences in the utilization and requirements of macro and micro nutrients. A detailed understanding of these interactions is essential to devise next-generation public health policy regarding nutritional requirements. 

Since metabolic homeostasis involves multiple organs, an imbalance in one system affects others leading to a domino effect on multiple organs. To elucidate the effects of nutrient-metabolic interactions, a systems level approach that integrates multiple organ systems, which takes into account differential molecular changes in organ systems is required. Moreover, unraveling the cause-effect relationship between the organ specific molecular functions and the overall physiological output is essential to develop technologies and pharmaceuticals to advance public health. 

We use genomics and molecular biology tools to elucidate the effect of nutrient-metabolic interactions in multiple organ systems including skeletal muscle, liver, intestine bones, and immune system using vitamin D metabolism as a model system. The following broad areas are being addressed in the lab

Maintenance of metabolic homeostasis by vitamin D

 Metabolic regulation of gene expression in immune cells

Regulation of protein synthesis in Mycobacterium tuberculosis
Apart from the nutrient-metabolism interactions in mammals, we also address how gene expression is regulated in human pathogen Mycobacterium tuberculosis. Though approximately 25% of the human population is expected to be infected with Mycobacterium tuberculosis, only 10% of them, based on their immune and metabolic status manifest the pathology. While modulation of protein synthesis has been implicated in pathogenicity, the mechanisms are unknown. We address various mechanisms by which M. tb protein synthesis is regulated to cope with host induced stress conditions.

Selected Publications

  • Umar D, Das A, Gupta S, Chattopadhyay S, Sarkar D, Mirji G, Kalia J, Arimbasseri GA, Durdik JM, Rath S, George A, Bal V. (2020) Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway. Proc Natl Acad Sci U S A. DOI: 10.1073/pnas.1922683117 (PMID: 32839313)
  • Chawla AS, Khalsa JK, Dhar A, Gupta S, Umar D, Arimbasseri GA, Bal V, George A, Rath S. (2020) A role for cell-autocrine interleukin-2 in regulatory T-cell homeostasis, Immunology, 160(3):295-309. doi: 10.1111/imm.13194 (PMID: 32187647)
  • Dhar A, Chawla M, Chattopadhyay S, Oswal N, Umar D, Gupta S, Bal V, Rath S, George A, Arimbasseri GA, Basak S. (2020) Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation. Sci Rep. 9(1):13867. doi: 10.1038/s41598-019-50454-z (PMID: 31554891)
  • Bhalla P, Shukla A, Vernekar DV, Arimbasseri AG, Sandhu KS, Bhargava P.  (2019) Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes. Sci Rep., 9(1):12892. doi: 10.1038/s41598-019-49316-5
  • Khalsa JK, Chawla AS, Prabhu SB, Vats M, Dhar A, Dev G, Das N, Mukherjee S, Tanwar S, Banerjee H, Durdik JM, Bal V, George A, Rath S*, Arimbasseri GA*. Functionally significant metabolic differences between B and T lymphocyte lineages. Immunology. 158(2):104-120. doi: 10.1111/imm.13098 (PMID: 31318442) *co-corresponding author
  • Arimbasseri GA. (2018) Interactions between RNAP III transcription machinery and tRNA processing factors. Biochim Biophys Acta Gene Regul Mech.  1861(4):354-360. doi: 10.1016/j.bbagrm.2018.02.003 (PMID: 29428193)

Selected postdoctoral publications 

  • Mattijssen S, Arimbasseri AG, Iben JR, Gaidamakov S, Lee J, Hafner M, Maraia RJ. (2017) LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection. Elife. 6. pii: e28889. doi: 10.7554/eLife.28889. (PMID:28895529)
  • Arimbasseri AG, Iben JR, Wei F, Rijal K, Tomizawa K, Hafner M and Maraia RJ. (2016) Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer require N6-isopentenylation of A37. RNA. 22(9): 1400-1410 (PMID: 27354703)
  • Arimbasseri AG and Maraia RJ. (2016) RNA Polymerase III advances: Structural and tRNA functional views. Trends in Biochemical Sciences. 41(6): 546-559 (PMID: 27068803)
  • Arimbasseri AG, Blewett NH, Iben J, Lamichhane TN, Cherkasova V, Hafner M, Maraia RJ. (2015) RNA polymerase III output is functionally linked to tRNA dimethyl-G26 modification. PLoS Genetics. 11(12): e1005671. (PMID: 26720005). a. Accompanying Perspective by M. Boguta, PLoS Genetics 11(12): e1005743
  • Arimbasseri AG and Maraia RJ. (2015) Mechanism of transcription termination by RNA polymerase III utilizes a nontemplate-strand sequence-specific signal element. Molecular Cell. 58(6): 1124-1132. (PMID: 25959395) a. Accompanying Preview by Artsimovitch & Belogurov, Molecular Cell 58(6): 974-976.
  • Arimbasseri AG, Kassavetis GA and Maraia RJ. (2014) Comment on Mechanism of eukaryotic RNA polymerase III transcription termination. Science. 345(6196): 524. (PMID: 25082694)
  • Rijal K, Maraia RJ and Arimbasseri AG* (2015) A methods review on use of nonsense suppression to study 3' end formation and other aspects of tRNA biogenesis. Gene 556(1): 35-50. (PMID: 25447915) (* Corresponding author)
  • Arimbasseri AG and Maraia RJ (2013) Distinguishing core and holoenzyme mechanisms of transcription termination by RNA polymerase III. Mol Cell Biol. 33(8): 1571-1581 (PMID: 23401852)

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