IISER MOHALI

Professor , Biological Sciences

Email

guptasarma(AT)iisermohali.ac.in

Phone

+91 172 2293151

Fax

+91 172 2240266

Personal Page

 www.guptasarmalab.in

Research Area

Protein Engineering & Structural Biochemistry

INTERESTS: My main interests lie in understanding and engineering the manner in which globular proteins fold; in why (and how) they misfold; in what these misfolded forms do (to cause human disease) or can be made to do (e.g., conduct electricity); in what determines the thermodynamic and kinetic stabilities of the folded, native forms of globular proteins (especially those evolved to function in extremophile microbes); and in developing approaches through which the activities and functions of globular proteins and enzymes can be altered through rational and/or combinatorial mutagenesis.

APPROACHES: I commonly employ (and also occasionally develop) preparative and analytical methods/approaches deriving from different forms of electronic and vibrational spectroscopy, mass spectrometry, biomolecular chromatography, electrophoresis, computation, calorimetry, microscopy, and recombinant DNA-based experimentation, and also certain other tools/techniques of organic and physical biochemistry.

ET CETERA: In addition, I also love to dwell upon (and occasionally contribute to) current understanding of the mechanistic basis of regulation of gene expression, and the cellular and molecular basis of development.

Selected Publications

• Sharma P, Kaila P, Guptasarma P. (2016). Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases. FEBS Journal 283, 4340-4356.

• Khan JM, Sharma P, Arora K, Kishor N, Kaila P, Guptasarma P. (2016). The Achilles' Heel of "Ultrastable" Hyperthermophile Proteins: Submillimolar Concentrations of SDS Stimulate Rapid Conformational Change, Aggregation, and Amyloid Formation in Proteins Carrying Overall Positive Charge. Biochemistry 55, 3920-3936.

• Sharma P, Guptasarma P. (2017). Endoglucanase activity at a second site in Pyrococcus furiosus triosephosphate isomerase-Promiscuity or compensation for a metabolic handicap? FEBS Open Bio 7, 1126-1143.

• Arora K, Thakur B, Mrigwani A, Guptasarma P. (2021). N-Terminal Extensions Appear to Frustrate HU Heterodimer Formation by Strengthening Intersubunit Contacts and Blocking the Formation of a Heterotetrameric Intermediate. Biochemistry 60, 1836-1852.

• Thakur B, Arora K, Gupta A, Guptasarma P. (2021). The DNA-binding protein HU is a molecular glue that attaches bacteria to extracellular DNA in biofilms. Journal of Biological Chemistry 296, 100532.

Associate Professor , Biological Sciences

Email

sudip(AT)iisermohali.ac.in

Phone

+91 172 2293168

Fax

+91 172 2240266

Personal Page

Research Area

Molecular Cell & Developmental Biology

Research Focus

Mitochondrial biology is a fast growing area in genetics and medicine, linking cell biological processes to metabolic disorders and cancer. The mitochondrion is not only the hub for energy generation; it is also a major site for other biosynthetic activities. Recent studies have demonstrated that mitochondria integrate diverse extra and intra cellular signals to regulate several cellular functions. We are interested in understanding the role of the mitochondrion in controlling cell biological processes like proliferation, growth and differentiation. We use the model organism, Drosophila melanogaster, for genetic dissection of retrograde signaling pathways from mitochondria to nucleus that are essential in modulating cellular responses. Our laboratory has a large collection of mutations in genes that code for mitochondrial proteins in Drosophila. Taking advantage of the advanced genetic tools available in this model system and using high-end microscopy and molecular genetic approaches we aim to unravel the mechanistic basis of mitochondrial regulation of cellular functions.

The other focus of our research involves embryonic stem cells. Embryonic stem cells, by virtue of their capacity to proliferate indefinitely and to differentiate into almost all types of somatic cells, hold the potential to be used for therapeutic purposes. Current research in this field aims to a) develop means to direct embryonic stem cells to differentiate into specific cell types that can be used for therapy and (b) to reprogram adult somatic cells to form induced pluripotent stem (IPS) cells. In this pursuit scientists are trying to understand the genetic regulations and modifications in the genome that contribute to the processes of reprogramming and differentiation. Although it is equally important to understand how these processes are affected by the cellular metabolic state, very limited studies address this issue. We aim to understand the mitochondrial control of proliferation and early lineage specification of ESCs. To achieve this goal we employ a combination of microscopic, histological, biochemical, genetic and molecular biology approaches.

Selected Publications

• Mandal S, Lindgren AG, Srivastava AS, Clark AT, Banerjee, U. (2011), Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells. Stem Cells, March; 29: 486–495.

• Mandal S, Freije WA, Guptan P, Banerjee U. (2010) Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system J Cell Biol. Feb; 188(4):473-9.

• Owsu-Ansah E, Yaveri A, Mandal S, Banerjee U (2008) Distinct mitochondrial retrograde signals activate the G1-S checkpoint Nature Genetics March; 40 (3): 356-361

• Liao TS, Call GB, Guptan P, Cespedes A, Marshall J, Yackle K, Owusu-Ansah E, Mandal S, Fang QA, Goodstein GL, Kim W, Banerjee U. (2006) An efficient genetic screen in Drosophila to identify nuclear-encoded genes with mitochondrial function Genetics. Sep; 174 (1): 525-533.

• Mandal S, Guptan P, Owusu-Ansah E, Banerjee U. (2005) Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila Developmental Cell. Dec; 9(6): 843-854.

Associate Professor, Biological Sciences

Email

lolitika(AT)iisermohali.ac.in

Phone

+91 172 2293172

Fax

+91 172 2240266

Personal Page

Research Area

Developmental Genetics

Research Focus

Stem cells are the source of virtually all highly differentiated cells that are replenished during the lifetime of an animal. The critical balance between stem and differentiated cell populations is crucial for the long-term maintenance of functional tissue types. A microenvironment that is supportive of stem cells is commonly referred to as a stem cell niche. We have previously identified a hematopoietic niche within the Drosophila larvae. Due to the limited access of mammalian hemtopoietic niche this amenable system will allow us to unravel molecular regulation of stem cell progenitors and its relation with the niche. The power of Drosophila as a model organism is very well established, most notably its genetics and developmental biology. Taking advantage of these strengths our group aims to find novel genes and mechanisms controlling hematopoietic progenitors cell specification and differentiation. Given the high degree of conservation of blood development between Drosophila and the vertebrates, we hope that the ability to manipulate the function of such genes in Drosophila would aid in understanding function and dysfunction in human hematopoiesis.

Selected Publications

• Parvathy Ramesh, Nidhi Sharma Dey, Aditya Kanwal, Sudip Mandal, Lolitika Mandal. (2021) Relish plays a dynamic role in the niche to modulate Drosophila blood progenitor homeostasis in development and infection. eLife 2021;10:e67158. DOI: https://doi.org/10.7554/eLife.67158.

• Aditya Kanwal, Pranav Vijay Joshi, Sudip Mandal, Lolitika Mandal (2021). Ubx- Collier     signaling cascade maintains blood progenitors in the posterior lobes of the Drosophila larval lymph gland. PLoS Genetics 17(8): e1009709. https://doi.org/10.1371/journal. pgen.1009709.

• Satish Kumar Tiwari, Ashish Ganeshlalji Toshniwal, Sudip Mandal and Lolitika Mandal. (2020). Fatty acid β-oxidation     is required for the differentiation of larval hematopoietic progenitors in Drosophila. eLife 2020;9:e53247 DOI: 10.7554/eLife.53247.

• Kaur H, Sharma SK, Mandal S, Mandal L. (2019) Lar maintains the homeostasis of the hematopoietic organ in Drosophila by regulating insulin signaling    in the niche. Development. Dec 23;146(24). pii: dev178202. doi: 10.1242/dev.178202.

• Sharma SK,    Ghosh S, Geetha AR, Mandal S, Mandal L. (2019)    Cell Adhesion- Mediated Actomyosin Assembly Regulates the  Activity of Cubitus Interruptus for Hematopoietic    Progenitor Maintenance in Drosophila. Genetics. Aug;212(4):1279-1300. doi: 10.1534/genetics.119.302209.

• Sharma N, Ramesh    P, Chugh M, Mandal S and Mandal L. (2016). Decapentapelagic dependent HSCs give rise to Hedgehog dependent blood progenitors in larval lymph     gland of Drosophila. eLife, 10.7554/eLife.)

• Ghosh S, Singh A, Mandal S and Mandal    L. (2015). Active Hematopoietic Hubs in Drosophila Adults generate hemocytes and contribute to immune response. Developmental Cell, 2015, 33: 478-488.
  

Associate Professor , Biological Sciences

Email

sandhuks(AT)iisermohali.ac.in

Phone

+91 172 2293182

Fax

+91 172 2240266

Personal Page

My Webpage                                    

Research Area

Systems biology of genome regulation

Research Focus

We are keen to address the fundamental questions pertaining to genome organization and regulation using systems approach. The boom in the whole genome studies has created a wealth of data, which allows us to test our hypotheses using computational methods and follow up with appropriate experiments.In particular, we are interested in following questions:

Why does the eukaryotic genome fold in a particular conformation, but not the other? What are the underlying evolutionary constraints? The present understating on this is too abstract.
How does the chromatin mobility associate with the regulation of essential genomic functions like transcription, replication and DNA repair? Some of our recent analyses contradict the presumption that loci with higher transcription have greater mobility.
How does the foreign DNA impact the 3D genome organization of the host cell? Does the viral DNA have preferred 3D interactions with host genome?
How is the intrinsic noise regulated in the cells? Does it associate with higher order chromatin states? Does it have any role in cell fate decision during lineage specification? Does it contribute to persistence of persister cells and can it be modulated synthetically?

Selected Publications

• Sandhu KS*, Guoliang Li1, Huay Mei Poh1, Yu Ling Kelly Quek1, Yee Yen Sia1, Su Qin Peh1, Fabianus Hendriyan Mulawadi1, Mile Sikic2, Francesca Menghi1, Anbupalam Thalamuthu1, Wing Kin Sung1, Xiaoan Ruan1, Melissa Jane Fullwood1,3, Edison Liu1,4, Peter Csermely5, Yijun Ruan1* Large scale functional organization of long-range chromatin interaction networks Cell reports (in press, *corresponding author).

• Li G#, Ruan X#, Auerbach RK#, Sandhu KS#, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, Sim HS, Peh SQ, Mulawadi FH, Ong CT, Orlov YL, Hong S, Zhang Z, Landt S, Raha D, Euskirchen G, Wei CL, Ge W, Wang H, Davis C, Fisher-Aylor KI, Mortazavi A, Gerstein M, Gingeras T, Wold B, Sun Y, Fullwood MJ, Cheung E, Liu E, Sung WK, Snyder M*, Ruan Y*. Extensive promoter centered chromatin interactions provide the architectural basis for transcription regulation in eukaryotes.Cell. 2012 Jan 20;148(1-2):84-98 (#joint first author)

• Sandhu KS*. Did the modulation of expression noise shape the evolution of three dimensional genome organizations? Nucleus. 2012; 3:3, 1-4 (*corresponding author)

• Sandhu KS, Shi C, Sjolinder M, Zhao Z, Gondor A, Liu L, Tiwari VK, Guibert S, Emilsson L, Imreh MP, Ohlsson R*. Nonallelic transvection of multiple imprinted loci is organized by the H19 imprinting control region during germline development. Genes Dev. 2009; Nov 15; 23: 2592-2597.

• Zhao Z, Tavoosidana G, Sjolinder M, Gondor A, Mariano P, Wang S, Kanduri C, Lezcano M, Sandhu KS, Singh U, >Pant V, Tiwari V, Kurukuti S, Ohlsson R*. Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet. 2006 Nov;38(11):1341-7.

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