Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PhD Project Template Use one form per project Please complete & submit to international@nuigalway.ie as soon as possible, and by 27/11/2012 In your email, begin the subject line with [SWB] (be sure to use square brackets) to ensure that your email is filed correctly. Emails will be automatically filed PI name & contact details: School: Corrado Santocanale -Prof. of Molecular Medicine and SFI Principal Investigator Centre for Chromosome Biology and National Centre for Biomedical Engineering and Science National University of Ireland, Galway University road, Galway, Ireland Phone:+353-(0)91-495174 Email: corrado.santocanale@nuigalway.ie School of Natural Sciences Has project been agreed with head (or nominee) of proposed registration school? Research Centre / group affiliation: Research group / centre website: Centre for Chromosome Biology, National Centre for Biomedical Engineering and Science http://www.chromosome.ie http://ncbes.eurhost.net/ PI website / link to CV: http://www.chromosome.ie/researchers/santocanale/ http://ncbes.eurhost.net/bio/corrado-santocanale.aspx Brief summary of PI research / research group / centre activity (2 or 3 lines max): If you are already involved in relevant scholarly activities relating to Brazil, please mention them here. Our laboratory is interested in studying the mechanisms that regulate genome replication in human cells with particular emphasis on the Cdc7 kinase and in exploiting the results of this research for therapeutic purposes. Cdc7 acts as a molecular switch for DNA synthesis and is also thought to participate in several other processes that regulate normal cell cycle progression and chromosome dynamics. Cdc7 inhibitors have promising anticancer activity in preclinical models and are under investigation as experimental drugs in humans. By undestanding how Cdc7 kinase functions at the molecular level we will increase our knowledge of DNA replication as well as help to define the mechanism of action of newly developed Cdc7 inhibitors and how their effectiveness could be increased. Title & brief description of PhD project (suitable for publication on web): Regulation of Cdc7 protein kinase by protein-protein interactions. The duplication of the genetic information is a crucial step that must be carried out correctly to Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras prevent cancer. Defects in the regulation of DNA duplication or in the replication machinery itself have been found in multiple cancer types. Cdc7 kinase is a key regulator of DNA synthesis and a new target for drug discovery in Oncology. In order to fully understand Cdc7 function we have adopted a mass spectrometry / proteomic approach and identified novel Cdc7 interacting proteins. Among these we found well validated Cdc7 interacting proteins as well as novel uncharacterized proteins. We will test the hypothesis that novel proteins regulate Cdc7 kinase activity and its functions and are important for cellular proliferation and for the response to replication stress. The expression of selected genes coding for Cdc7 interactors will be down-regulated by molecular genetics tools (e.g. siRNA transfection) and the effects on cell viability, DNA replication and the response to genotoxic agents assessed. Unique selling points of PhD project in NUI Galway: This project will allow the student to access the NUIG mass spectrometry facility, directed by the the PI (Corrado Santocanale), and to receive specific training in techniques related to proteomics. Multidisciplinary approaches and the use of Molecular Biology, Cell Biology and Analytical Biochemistry techniques will be an essential part of the project. The student will be integrated within the Centre of Chromosome Biology. S/He will present and discuss results/progress regularly thus receiving essential feedback and support from approximately 70 scientists (including 11 PIs)with expertise in related fields of investigation. Name & contact details for project queries, if different from PI named above: Please indicate the graduates of which disciplines that should apply: Biochemistry, Genetics, Molecular Biology, Biotechnology Ciência sem Fronteiras / Science Without Borders Priority Area: Please indicate the specific programme priority area under which the proposed PhD project fits- choose only one (tick box): Engineering and other technological areas Pure and Natural Sciences (e.g. mathematics, physics, chemistry)/Physical Sciences (Mathematics, x Physics, Chemistry, Biology and Geosciences) Health and Biomedical Sciences / Clinical, Pré-clinical and Health Sciences Information and Communication Technologies (ICTs), Computing Aerospace Pharmaceuticals Sustainable Agricultural Production Oil, Gas and Coal Renewable Energy Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras Minerals, Minerals Technology Biotechnology Nanotechnology and New Materials Technologies for Prevention and Mitigation of Natural Disasters Bioprospecting and Biodiversity Marine Sciences Creative Industry New technologies in constructive engineering Please indicate which of the following applies to this project (referring to Science Without Borders arrangements): Suitable only as a Full PhD (Y/N): _ _Y___ Available to candidates seeking a Sandwich PhD arrangement (Y/N): _N____ Suitable for either/Don’t know: _____