Assistant Prof Amartya Sanyal

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Assistant Professor Amartya Sanyal, PhD
Nanyang Assistant Professor, School of Biological Sciences and Lee Kong Chian School of Medicine,
Nanyang Technological University
Email: asanyal@ntu.edu.sg
Principal Investigator, 3D CATG (Chromatin Architecture, Transcription and Genomics) Laboratory
Webpage: http://www.ntu.edu.sg/home/asanyal
 
 
 
Introduction

Assistant Professor Amartya Sanyal is a Nanyang Assistant Professor at School of Biological Sciences and Lee Kong Chian School of Medicine. Asst Prof Sanyal obtained his PhD from Indian Institute of Science, Bangalore, working on human germ cell gene expression and their regulation during spermatogenesis. He then moved to University of Massachusetts Medical School, Worcester, USA, for his postdoctoral training under the supervision of Dr Job Dekker who pioneered the Chromosome Conformation Capture (3C) technique.

Being a part ENCODE (ENCyclopedia Of DNA Elements) consortium project, which is funded by National Human Genome Research Institute,Asst Prof Sanyal successfully generated high-resolution 3D chromatin interaction map and comprehensively annotated long-range chromatin interactions of gene promoters in 1% of human genome using high throughput 3C-based method combined with next-generation sequencing (NGS). Asst Prof Sanyal’s work has been published in leading research journals and is highly cited. He worked in close collaboration with several reputed laboratories at University of Washington, Stanford University, Emory University, and etc. Asst Prof Sanyal’s research has made significant impact in the understanding of 3D genome organisation and chromatin looping interactions. He had also been selected for the prestigious Wellcome Trust/DBT India Alliance Intermediate Fellowship in 2014.


Research Focus
The main focus of Asst Prof Sanyal’s laboratory is to understand 3D genome organisation inside the nucleus and its impact on transcriptional regulatory code during mammalian development, differentiation and disease. The laboratory employs high-throughput genomic methods, genome-editing and imaging techniques in combination with bioinformatics and computational approaches to understand structure-function relationship of chromatin.

Gene regulation in three dimensions

Human genome is organised in highly complex conformations inside the nucleus. How this three-dimensional organisation of chromatin affects biological processes like gene regulation is largely unknown. The effects of regulatory elements like enhancers are known to be important for transcriptional regulation. Comprehensive genome-wide annotations, using various chromatin features and binding of trans-factors, have helped to ‘identify’ the distal regulatory elements, however they do not give an insight into the connection between a particular regulatory element and its target gene(s). The advent of Chromosome Conformation Capture (3C)-based techniques and its high-throughput adaptations have made it possible to generate genome-wide spatial proximity map of chromatin as well as to detect specific long-range looping interaction between genomic elements, for example between enhancer and promoter, at high-resolution.​

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Figure 1: Genes and their regulatory elements may have complex 3D relationships
3D genome organisation and disease

The proper functioning of biological processes require regulated expression of cell- and tissue-specific genes. This precise gene regulatory program is influenced by 3D chromatin architecture, chromatin features, epigenetic mechanisms (histone modifications, DNA methylation etc) and binding of trans-acting factors.  Any defects in this regulation will lead to disease conditions. In the past decade, genome-wide scans of SNPs (single nucleotide polymorphisms) in populations have identified many genomic loci associated with predisposition to disease. The observed associations are possibly driven by linkage disequilibrium with the disease-associated region in vicinity. However, majority of SNPs identified by genome-wide association studies (GWAS) do not map to coding regions, suggesting that these regions may, in fact, affect gene regulatory mechanisms and may be involved in controlling the expression of distal target genes, the identity of which remains unknown. Therefore, connecting the GWAS SNPs to their target genes would aid in understanding genotype-phenotype relationships in disease, and in designing effective treatment and therapeutics. 

Overall, Asst Prof Sanyal’s laboratory is interested in deciphering the gene regulatory mechanisms of cell- and tissue-specific gene expression in relation to 3D chromatin architecture, epigenetic mechanisms (chromatin modifications) and binding of trans-acting factors to understand various biological processes in normal and disease conditions. Efforts will also be focused on understanding how non-coding sequence variants identified by GWAS contribute to disease risk and pathogenesis.


Key Publications

  1. Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR, Bell JS, Ong CT, Hookway TA, Guo C, Sun Y, Bland MJ, Wagstaff W, Dalton S, McDevitt TC, Sen R, Dekker J, Taylor J, Corces VG. (2013). Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell. 153(6):1281-95.
  2. Ferraiuolo MA, Sanyal A, Naumova N, Dekker J, Dostie J. (2012).  From cells to chromatin: Capturing snapshots of genome organization with 5C technology. Methods. 58(3):255-67.
  3. Sanyal A*, Lajoie BR*, Jain G, Dekker J. (2012). The long-range interaction landscape of gene promoters. Nature. 489(7414):109-13. (*equal contributions)
  4. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, John S, Sandstrom R, Bates D, Boatman L, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee BK, Lee K, London D, Lotakis D, Neph S, Neri F, Nguyen ED, Qu H, Reynolds AP, Roach V, Safi A, Sanchez ME, Sanyal A, Shafer A, Simon JM, Song L, Vong S, Weaver M, Yan Y, Zhang Z, Zhang Z, Lenhard B, Tewari M, Dorschner MO, Hansen RS, Navas PA, Stamatoyannopoulos G, Iyer VR, Lieb JD, Sunyaev SR, Akey JM, Sabo PJ, Kaul R, Furey TS, Dekker J, Crawford GE, Stamatoyannopoulos JA. (2012). The accessible chromatin landscape of the human genome. Nature. 489(7414):75-82.
  5. ENCODE Project Consortium, et. al. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature​. 489(7414):57-74.
  6. ENCODE Project Consortium, et. al. ( 2011). A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9(4):e1001046.
  7. Sanyal A, Baù D, Martí-Renom MA, Dekker J. ( 2011). Chromatin globules: A common motif of higher order chromosome structure?. Curr Opin Cell Biol. 23(3):325-31.
  8. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY. (2011). A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 472(7341):120-4.
  9. Baù D*, Sanyal A*, Lajoie BR*, Capriotti E, Byron M, Lawrence JB, Dekker J, Marti-Renom MA. ( 2011). The three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules. Nat Struct Mol Biol. 18(1):107-14.  (*equal contributions)
  10. Lajoie BR, van Berkum NL, Sanyal A, Dekker J. (2009). My5C: Web tools for chromosome conformation capture studies. Nat Methods. 6(10):690-1.