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Laboratory of Genome Architecture
& DNA topology 

The Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.

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Research

DNA folding and organization within a tiny nucleus have fascinated researchers for several decades. Recent studies have shown the importance of genome organization in the regulation of gene expression, DNA replication, recombination, and cell division.  Recent developments in the ‘chromosome conformation capture (3C) technique have revealed details of genome organization particularly in the context of human diseases. Genomic rearrangements, a common feature of the cancer genome, often disorganized higher order of genome organization leading to suppression of tumor suppressors or oncogenic gene expression.  However, unraveling the pathogenicity associated with the 3D genome still remains a challenge, as internal structures and elements contributing for the organization of the DNA within the nucleus are yet to be understood. Importantly, how chromatin compartments/domains are spatially formed within the nucleus and to what extent changes in domains cause gene miss-expression, is still an open question. By using integrated genomics approaches, we wish to decode mechanisms responsible for chromatin folding in three-dimensional space and how these features are deregulated during disease conditions

Dr. Yathish J. Achar

Head, Laboratory of Genome Architecture

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Ph.D.: University of Szeged, Szeged, Hungary.

Post Doc: IFOM Foundazione Istituto FIRC di Oncologia Moleculare, Milan, Italy

Yathish J Achar obtained his PhD from University of Szeged, Hungary, in the field of Biological sciences. As a graduate student he was involved in developing an in vitro system to study fork regression activities of several tumour suppressors including HLTF, BLM, WRN, SMARCAL1 and ZRANB3. Later, he moved to Marco Foiani laboratory in IFOM (Foundazione Istituto FIRC di Oncologia Moleculare), Milan, Italy, as a post-doctoral fellow. In IFOM he was involved in mapping DNA supercoil changes and its influence on chromatin organization using genomic approaches.

Recently, he joined CDFD as a group leader and his group’s research interest is to unravel the link between DNA mechanics and chromosomal organization with specific emphasis on cancer predisposition.

News & Anouncemnets

29th June 2022
Nilay Joined our team as a PhD student!

Open Positions

PhD positions available (November 2022 update)

We have two Ph.D. positions in experimental and computational genomics to understand genome organization.  We combine a great variety of genomics and molecular biology techniques with computational analysis using various systems including, embryonic stem cells, cancer cell lines, and human primary tumors. We are looking for highly motivated candidates who wish to obtain hands-on skills in advanced genomics approaches including, Hi-C, SPRITE, ChIP-Seq, DRIP-Seq, RNA-seq, and whole genome analysis. If interested get in touch with me (yathish@cdfd.org.in).

 

The last date for submitting the online application is December 14, 2022  

 

Further details on our research: Laboratory of Genome Architecture

 

For application details: http://cdfd.org.in/rsp/rsp-1_2023_advt.pdf

Latest Publications

Negative supercoil at gene boundaries modulates gene topology

Transcription challenges the integrity of replicating chromosomes by generating topological stress and conflicts with forks1,2. The DNA topoisomerases Top1 and Top2 and the HMGB family protein Hmo1 assist DNA replication and transcription3-6. Here we describe the topological architecture of genes in Saccharomyces cerevisiae during the G1 and S phases of the cell cycle. We found under-wound DNA at gene boundaries and over-wound DNA within coding regions. This arrangement does not depend on Pol II or S phase. Top2 and Hmo1 preserve negative supercoil at gene boundaries, while Top1 acts at coding regions. Transcription generates RNA-DNA hybrids within coding regions, independently of fork orientation. During S phase, Hmo1 protects under-wound DNA from Top2, while Top2 confines Pol II and Top1 at coding units, counteracting transcription leakage and aberrant hybrids at gene boundaries. Negative supercoil at gene boundaries prevents supercoil diffusion and nucleosome repositioning at coding regions. DNA looping occurs at Top2 clusters. We propose that Hmo1 locks gene boundaries in a cruciform conformation and, with Top2, modulates the architecture of genes that retain the memory of the topological arrangements even when transcription is repressed.

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