Senior Scientist
Centre for Cellular and Molecular Biology
Uppal Road
Hyderabad 500 007
India.
Email: mishra@ccmb.res.in
Telephone: (+ 91) 40 2719 2658
Fax No: (+ 91) 40 2716 0591
Our lab is interested in higher order chromatin structure in the context of genomic organization and regulation of gene expression.
1 Chromatin and nuclear architecture
Establishment of cell type specific gene expression and epigenetic inheritance of the expression state are essential features of developmental mechanisms. We are studying these processes at the level of higher order chromatin organization. We focus on the following:
1.1 Molecular analysis of boundary and Polycomb response elements
1.2 The Nuclear matrix
1.3 Genomic organization and chromatin structure in the human Y chromosome
2 Homeotic gene complexes: the evo-devo of A-P body axis
Homeotic gene complexes determine the A-P body axis in animals. Expression and function of the homeotic genes along the A-P axis is colinear with their order of occurrence in the complex. This 'chromosomal organization and its functional correspondence' is conserved during evolution. We are studying the molecular basis of this conservation and mechanisms involved in the regulation of the Hox complexes:
2.1 Regulation of bithorax complex of Drosophila melanogaster
2.2 Evolutionarily conserved features in the organization and regulation of Hox complexes
3 Comparative genomics of non-coding DNA
In higher eukaryotes a large proportion of the genome does not code for proteins. It is emerging that a large proportion of non-coding DNA is required for packaging and regulation of the genome. We believe that genomes evolve within this constraint of packaging. The 'packaging code' of genomes is not clear as yet. We have taken comparative genomics approach to study patterns with in the non-coding regions, in particular the stretches that are under strong selection pressure:
3.1 Comparative and functional genomics of non-repetitive non-coding DNA
3.2 Pattern search approach to identify novel regulatory elements
Current Lab Members
Name Position
Rakesh K Mishra Senior Scientist
Rashmi U Pathak Scientist
A.Srinivasan Technical Assistant
Afsar Soghra Secretariat
M.Anitha Postdoctoral Fellow
D.Vasanthi PhD Student
S.Krishnan PhD Student
Ram P Kumar PhD Student
Bony De Kumar PhD Student
Hina Sultana PhD Student
Navneet K M PhD Student
Satish Kallappagoudar PhD Student
R Senthilkumar PhD Student (Joint PhD program of CCMB & IIIT-H)
Narendra Pratap Singh PhD Student
Abhishek Kulkarni PhD Student
Sreesankar E PhD Student (CSIR sponsored collaborative project with University of Hyderabad)
Manohar Dange Project JRF (CSIR sponsored collaborative project with University of Hyderabad)
Jyotsna Singh Project JRF
Sayantanee Dutta Project JRF
Rakesh Mishra's Lab in CCMB
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His wife Dr.KRISHNAVENI MISHRA also assit professor in UNIVERSITY of hyderabad.
DR KRISHNAVENI MISHRA
Contact: kmsl.@.uohyd.ernet.in, +91-40-23134572 (Tel); +91-40-23010120 (Fax)
Dr Krishnaveni Mishra PhD (CCMB, JNU)
Lecturer.
Teaching: Genetics, Genetic engineering, Microbiology, Lipid biochemistry
Research Interest: Functional Compartmentalization of the Nucleus and Telomere biology
The eukaryotic nucleus is organized into various compartments, several of these are readily visible under the microscope, like the nucleolus, nuclear lamina, etc. Apart from these prominent structures, several nuclear functions like transcription, splicing, DNA repair seem to be restricted to certain distinct loci within the nucleus. Additionally, current data support the view that the nucleus is subdivided into transcriptionally permissive and restrictive compartments. Importantly, there is a lot of reorganization at the nuclear level during differentiation. These observations strengthen the view that nuclear compartmentalization has consequences on the functioning of the genome.
My lab is using the budding yeast as a model system to study the establishment and maintenance of telomere-based compartments at the nuclear periphery. Telomeres are ends of the chromosomes consisting of tandem repetitive sequences and specific set of proteins associated with it. The telomere repeat tracts are maintained by telomerase, a telomere specific reverse transcriptase that counteracts the loss of terminal sequences during DNA replication. Telomeres also protect chromosome ends from fusion and prevent the natural chromosome ends from being recognized as double strand DNA breaks by the DNA repair system. The 32 telomeres of budding yeast are confined to a few foci at the periphery of the nucleus that light up as 3-6 intensely staining spots when hybridized with fluorescently labeled telomeric DNA. These foci recruit and accumulate the SIR (silent information regulator) proteins and create a transcriptionally repressive environment at the nuclear periphery.
A few proteins involved in DNA repair (eg Yku70, Yku80) are also found in this foci. Certain conditions like, large number of DNA breaks, aging etc induce the movement of Sirp from the telomeres. Several questions remain unanswered. How are the telomeres clustered and anchored to the nuclear periphery? What is the molecular basis of this organization? What happens to these sites during cell division and differentiation? What is the connection between these sites and telomere synthesis, DNA repair, aging etc.
We have taken a genetic and cell biological approach to address these issues. We are isolating mutants that disrupt the establishment and maintenance of these compartments in order to understand the molecular basis of this compartmentalization. We are also taking a bioinformatics approach to look at the sequences at the subtelomeric regions to see if there are any signature sequences that contribute to this organization. We are tagging individual chromosomes with traceable markers to investigate the specificity of these associations. Additionally, we are investigating the connection between telomere metabolism, DNA repair and nuclear compartmentalization.
Significant Publications
Pathak, R.U., Ragaraj, N., Sathish, K., Mishra, K*., and Mishra, R. (2007). Boundary Element Associated Factor, BEAF 32B, Connects Chromatin Domains to the Nuclear Matrix. Mol. Cell. Biol. 27: 4796-4806. (*Corresponding author)
Krishnaveni Mishra, Vivek S Chopra, A. Srinivasan and Rakesh Mishra. Trl-GAGA interacts with lola -like and both are part of the repressive complex of Polycomb group of genes. Mechanisms of Development.120: 681 – 689. 2003.
Krishnaveni Mishra and David M. Shore. Yeast Ku protein plays a direct role in telomeric position effect and counteracts the inhibitory effects of rif proteins. Curr. Biology 9, 1123-1126, 1999.
Krishnaveni Mishra and Veena K. Parnaik. Essential role of protein phosphorylation in nuclear transport. Expt. Cell Res. 216, 124-134, 1995.
Krishnaveni Mishra, DVSS Kathyayini and Veena K. Parnaik. A conserved epitope on pore phosphoproteins reflects cell division status. Indian J. Biochem. Biophysics 31, 243-248, 1994.
Siyaram Pandey, Anjali S. Karande, Krishnaveni Mishra and Veena K. Parnaik. Inhibition of nuclear protein import by an antibody that recognises a novel class of pore proteins. Expt. Cell Res. 212, 234-254, 1994.
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1 comment:
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