Lining up the key players....building the strongest team

OU researchers are investigating the structural role of chromatin in eukaryotic transcription.

This research is being carried out by Manjunatha Shivaraju, an Open University PhD student who is based at the Stowers Institute for Medical Research, USA.

Chromosomes are not passive carriers of the genomic information. Instead, their structure changes throughout the cell cycle and they acquire distinct features that allow the timely expression of this information, preserve genome stability and ensure its faithful transmission. Histones are groups of simple alkaline proteins usually occurring in cell nuclei, which combine ionically with DNA (deoxyribonucleic acid) to form nucleoproteins. Histones mediate DNA organisation and play a dominant role in regulating eukaryotic transcription. As fundamental structural components of chromatin they are known to play an important role in chromosome dynamics and segregation.

Cse4, a histone H3 variant, is a structural component of the core centromere of S. cerevisiae. We have been working towards understanding the structural and functional role of Cse4 in the fidelity of chromosome distribution. This histone variant marks the centromeric chromatin in eukaryotes and delineates the site of formation of the kinetochore, a protein structure that attaches chromosomes to microtubules. Scm3 is a newly identified protein that immunopurifies with Cse4. Recent results show that Scm3 is vital for the formation of centromeric chromatin, a functional kinetochore, and subsequent chromosome segregation. In addition, Scm3 is required throughout the cell cycle to maintain a segregation-competent kinetochore. The present project proposes to define the precise molecular role of Scm3 through structural and functional analysis of Scm3 in the formation of Cse4-containing nucleosomes and subsequent kinetochore formation.

Manjunatha Shivaraju began his undergraduate career in agriculture at the University of Agricultural Sciences, Bangalore, India. The interface between science and society inspired Manjunatha to pursue his career in a subject that applied all the basic biological and chemical concepts together for the benefit of society. Manjunatha joined MSc (Agriculture) Plant Biotechnology, at the University of Agricultural Sciences, Bangalore, India. For his MSc thesis he worked on molecular marker (RAPD) in coconut and identified few molecular markers to yield and mite resistance. The results were published in the Jan 2007 issue of Genome.

After the MSc, Manjunatha worked as a junior research fellow in Chromatin Biology Laboratory (Professor MRS Rao), at Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India. During this time he worked to understand the nucleocytoplasmic transport of Transition protein2 in rat haploid germ cells. The results were published in the Aug 2007 issue of ‘Molecular and Cellular Biology’.
Manjunatha registered as a graduate student on the OU’s ARC programme OU in July 2007, in collaboration with the Stowers Institute for Medical Research where he is now based.

Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.

The Open University’s Affiliated Research Centre (ARC) programme came into effect on 1 October 2007 and is designed to ensure that we support the provision of doctoral training in the UK, Europe and worldwide. Through collaborative relationships with research institutions who do not have their own degree awarding powers we have created a network of partner organisations with interests which complement and extend our own strengths in life and biomolecular sciences, Earth and environmental sciences, and in some arts and humanities disciplines. Our partner institutions include: Architectural Association School of Architecture; HR Wallingford; KEMRI - Wellcome Trust Research Programme, Kenya; International Centre for Genetic Engineering and Biotechnology, Italy; Medical Research Laboratories, The Gambia; Royal Botanic Gardens, Kew and Stowers Institute for Medical Research, USA.

For more information see: http://www.open.ac.uk/research/research-degrees/affiliated-research-centre-programme/index.php