Career History
BA (Genetics) Trinity College Dublin
PhD University of Edinburgh (with Adrian Bird)
Post-Doc Fred Hutchinson Cancer Centre, Seattle (with Ron Reeder)
Lecturer/Senior Lecturer University of Dundee (Medical school)Research funded by Wellcome Trust project and MRC program grants Professor in Biochemistry NUI Galway (since Sept 2008)Research funded by SFI
Prof Brian McStayWellcome Trust Senior Investigator Award
April 2015- March 2020
Area of researchimportance of the candidate’s research questions
Chromosomal contextGenomic stability
Nucleolar fusion
Altered form and function of nucleoli in human disease
(Cancer and ribosomopathies)
Active v Silent Unsequenced
Our contributionsthe candidate’s track record and approach
Extensive binding of UBF across rDNA arrays defines active NORs
Active v Silent
Sullivan, G.J., Bridger, J.M., Cuthbert, A.P., Newbold, R.F., Bickmore, W.A. and McStay, B. (2001) EMBO J, 20, 2867-2874.
O'Sullivan, A.C., Sullivan, G.J. and McStay, B. (2002) Mol Cell Biol,22, 657-668.
Mais, C., Wright, J.E., Prieto, J.L., Raggett, S.L. and McStay, B (2005)Genes and Development, 19, 50-64.
Prieto, J.L. and McStay, B. (2007) Genes and Development, , 21, 2041-2054.
Integrate Mb arrays of artificial UBF binding sites
Novel 20 constrictions
appear?
Array is 1.4Mb
Pseudo-NORs
Our contributions
Grob, A., Colleran, C. and McStay, B. (2014) Genes and Development, 28, 220-230.
The neo-NOR cassette (20.4kb)
Human promoter
XEn elements
Mouse coding sequences
18S 5.8S 28S
Transcriptional terminator
5’ETS
ITS1 ITS2 3’ETS
By constructing synthetic nucleoli in human cells, neo-nucleoli, we were able to prove that nucleolar formation is a staged process where UBF-dependent mitotic bookmarking precedes
function-dependent nucleolar assembly.
Our contributions
~95% identical and high level segmental duplication
The first description of the genomic architecture of NORs
and surrounding sequences on acrocentric p-arms
>99% identical and unique to acrocentric p-arms
PJ DJ
Our contributions
Floutsakou, I., Agrawal, S., Nguyen, T.T., Seoighe, C., Ganley, A.R. and McStay, B. (2013) Genome Research, 23, 2003-2012.
A localized nucleolar damage response facilitates recruitment of the
homology directed repair machinery independent of cell cycle stage
Our contributions
van Sluis, M and McStay, B. (2015) Under revision for Genes and Development
• Contribute to completion of human genome and a description of its 4D organisation in human cells
Outcomes
• Finally describe the chromosomal context of NORs and how this influences the biology of nucleoli
• Provide new tools for nucleolar research and exploring its role in human disease
1. Genomic architecture of acrocentric p-arms
2. Regulation of NOR function and nucleolar morphology
3. Chromosomal context and genomic stability of NORs
Approaches
Genomics, Cell biology, Genome editing, Bioinformatics
Specific aims
The Genomic Architecture of Human NORs and its Role in Nucleolar Biology
Application Process
Motivations for application• the knowledge that our current work is our most important• advice from the CCB Scientific advisory board • the current funding climate in Ireland
1st Oct/2014Advised that the Wellcome Trust’s Molecular Basis of Cell Function Expert Review Group has considered my application and has recommended that it progress to interview by the Interview Panel
18th July/2014Submitted application for Senior Investigator Award , ‘The genomic architecture of human nucleolar organizer regions and its role in nucleolar biology . ’
27th Nov/2014Received comments from 4 referees
4th Dec/2014Interview
Questions asked of reviewers
• What is your view of the quality and importance of the candidate’s research questions?
• What is your view of the candidate’s approach?
• What is your view of the candidate’s track record, relative to his or her career stage?
• What is your view of the research environment?
• Overall Assessment
• Data Management and Sharing
Interview structure
The interview consists of a ten minute presentation of the research proposal followed by approximately twenty minutes of questions from the Panel.
The presentation is strictly limited to three slides, without any animation or movies. Cannot understate importance of the quality and preparedness of presentation.
The Interview Panel consists of a Co-Chair and core members. Additional individuals from the Expert Review Groups and other specialists may be invited, as appropriate, to join the Interview Panel for each round. In addition to Panel members, Wellcome Trust staff and Governors will be in attendance
Panel included 8 scientists (including at least 1 specialist), 4 from the US, 3 from the UK and 1 from GermanyQuestions arose from the presentation and from referees comments. No sense of outcome from the interview
Interview (Dec 4th)
Decision (Dec 12th)
Phone call informing me that I was successful, and that I would receive the full amount requested.Required to submit part B of application including the detailed budget.
Award Letter (Jan 23rd)
Funding details
Final Comment
The entire process focused on the science.
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