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Dr S Brogna Dr Aditi Kanhere No more applications being accepted Competition Funded PhD Project (European/UK Students Only)

Birmingham United Kingdom

About the Project

Gene expression is the process that leads from gene to active protein. The process involves three fundamental steps in eukaryotic organisms such as animals: transcription of DNA into RNA, processing of the primary transcript (pre-mRNA) and then translation of the mRNA into protein. Similar to other complex biochemical processes, the different steps of gene expression are coordinated in the cell. There are two levels of coordination; one involves coupling between the different biochemical reactions, for example, pre-mRNA processing reactions such as splicing of introns are coupled to transcription so that the newly synthesized RNA is still attached to the RNA polymerase while it is spliced; the other level of coordination requires synchronized expression of several genes to produce a given functional output. For example, the cell capacity to synthesize proteins is strictly dependent on the number of ribosomes present, so during growth the number of ribosomes must be doubled before cell division. The ribosome, however, is one of the most complex molecular machines in the cell, composed of about 80 different proteins and 4 RNAs. The building of such a complex machine requires synchronized expression of hundreds of genes. How cells achieve this level of synchronization is not well understood, particularly in multicellular organisms. This research project aims to understand these mechanisms in the fruit fly Drosophila melanogaster which is one of the most amenable model organisms used in many labs throughout the world. We envisage that the results of this research will advance our knowledge of basic cellular processes and, because about 70% of disease associated genes are conserved between Drosophila and humans, lead to a better understanding of human diseases, which, like cancer, are often the result of the failure of mechanisms that coordinate ribosome production with growth.

Funding Notes

This studentship is competition funded by the BBSRC MIBTP scheme: http://www.birmingham.ac.uk/research/activity/mibtp/index.aspx

Deadline: January 31, 2014

Number of Studentships available: 30

Stipend: £ 13,726 per annum (plus £600 travel allowance in year 1, and a MacBook Pro)

The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC-funded doctoral training partnership between the universities of Warwick, Birmingham and Leicester. It delivers innovative, world-class research training across the Life Sciences to boost the growing Bioeconomy across the UK.

To check your eligibility to apply for this project please visit: http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/

References

• Al-Jubran K.,Wen J., Chaudhury SR, Li M., Abdullahi A., Ramanathan P., Matina T., De S., Piechocki K., Rugjee KN and Brogna S. Visualization of the Joining of Ribosomal Subunits Reveals the Presence of 80S Ribosomes in the Nucleus. RNA 19: 1-16, 2013.

• Rugjee, K.N. Chaudhury, S.R., Al-Jubran, K., Ramanathan, P., Matina, T., Wen, J. and Brogna, S. Fluorescent protein tagging confirms the presence of ribosomal proteins at Drosophila polytene chromosomes. PeerJ, 2013, e15.

• De S, Brogna S. Are ribosomal proteins present at transcription sites on or off ribosomal subunits? Biochem Soc Trans. 38:1543-7. 2010.

• Brogna S, Sato T and Rosbash M.
Ribosome components are associated with sites of transcription
Molecular Cell 10:93–104. 2002.

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For more than a century, the University of Birmingham has been pursuing and sharing knowledge through outstanding teaching and research. As a founding Russell Group member and the original ‘redbrick’ university, our high-quality teaching will help you take your career to the next level. We are of the country’s most consistently sought-after universities by the UK’s top graduate employers, and have been for the last decade. With a wealth of opportunities to choose from across study and research, Birmingham has one of the most extensive postgraduate course portfolios in the UK. Hosting an international community of more than 8000 staff and 38,000 students, you’ll work alongside world-leading academics in a diverse community.

Career overview

Dr Saverio Brogna was born in Piscopio, Italy, where he completed his undergraduate studies in Biological Sciences at the University of Pavia (Collegio Ghislieri). After graduating, he worked for nearly three years in Iraklion, Crete, Greece, with Professor Babis Savakis. Dr Brogna then pursued his PhD and postdoctoral research in the Department of Genetics at Cambridge University under the supervision of Professor Michael Ashburner. In 2000, he was awarded a Wellcome Trust International Prize Travelling Fellowship to conduct research at Brandeis University in the USA with Professor Michael Rosbash. Dr Brogna joined the School of Biosciences at the University of Birmingham in 2000, initially on an independent Wellcome Trust fellowship, and subsequently received a Royal Society Research Fellowship from 2004 to 2013, which enabled him to establish his independent research group. His research focuses on RNA biology, particularly the mechanisms linking pre-mRNA processing with translation and Nonsense Mediated mRNA Decay (NMD), as well as the functions of ribosomes and ribosomal proteins within the nucleus.

Research interests

Dr Brogna''s research focuses on RNA biology, specifically the mechanisms connecting pre-mRNA processing with translation and Nonsense Mediated mRNA Decay (NMD). The laboratory investigates several aspects of RNA processing, primarily using the yeast *Schizosaccharomyces pombe* and the fruit fly *Drosophila melanogaster* due to their genetic advantages. A key area of interest is the mechanism of NMD, which plays a crucial role in the quality control of gene expression by degrading abnormal mRNAs with premature termination codons (PTCs). Dr Brogna''s work has revealed that PTCs significantly affect spliced mRNAs compared to transcripts from intron-less genes and can influence nuclear polyadenylation. The research aims to elucidate the interconnections between pre-mRNA processing, translation, and mRNA stability. Additionally, Dr Brogna''s group develops techniques to visualise the recruitment of processing factors to nascent transcripts, exploring how the composition of ribonucleoprotein complexes affects mRNA maturation pathways. Another focus is on visualising translation, where the group has tagged ribosomal subunits with fluorescent proteins to study their interactions in *Drosophila* cells, discovering the presence of translating ribosomes in the nucleus and seeking to identify associated RNAs.

RNA Biology Pre-mRNA Processing Translation Nonsense Mediated mRNA Decay Ribosomes Ribosomal Proteins Gene Expression Molecular Biology Cell Biology Eukaryotic Gene Expression mRNA Stability RNP Complexes Drosophila Schizosaccharomyces pombe Visualisation Techniques Quality Control of Gene Expression Transcription mRNA Export mRNA Localization Fluorescent Tagging Research Techniques

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BBSRC MIBTP - Understanding nuclear functions of ribosomal proteins in synchronising gene expression during growth.

University of Birmingham School of Biosciences

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About the Project

Funding Notes