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Prof Silvia Paracchini
No more applications being accepted
Funded PhD Project (Students Worldwide)
About the Project
Worldwide, 10% of people are left-handed and this population bias is a characteristic unique to human. Handedness can be considered a reflection of cerebral asymmetries where right-
handedness implies a dominance of the left hemisphere for motor function. A significant genetic component is implicated in handedness but little is known about the underlying molecular determinants. Recently we have identified the first genetic association with handedness at a genome-wide significance level (p < 5 × 10−7). The associated genetic markers lie within an intronic region of PCSK6, a gene known for its role in establishing left/right body asymmetries in early development and therefore a strong candidate for influencing handedness. Intriguingly, the association is specifically found in people with dyslexia.
The first aim of this project is to understand at a molecular level how genetic variation at the PCSK6 locus affects gene function. You will use different molecular biology techniques to study effects on gene expression and alternative splicing regulation, such as chromatin immuneprecipitation (ChIP) gene-reporter and gel-shift assays. Extensive use of bioinformatics and web-based resources will be employed to guide the experiments. The second aim is to elucidate the specificity of this association observed only in people with dyslexia. You will be part of a multidisciplinary team and will integrate your work with data from large genetic association studies and functional genomics resources. In particular you will be involved in evaluating the relevance of genexgene interactions and network pathways to explain phenotypic variation.
Key publications
Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Talcott JB, Stein J, and Monaco AP. (2011) PCSK6 is associated with handedness in individuals with dyslexia. Human Molecular Genetics, 20:608-614
Dennis MY, Paracchini S, Scerri TS, Prokunina-Olsson L, Knight JC, Wade-Martins R, Coggill P, Beck S, Green ED, and Monaco AP. (2009) A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene. PLoS Genetics, 5(3):e1000436.
handedness implies a dominance of the left hemisphere for motor function. A significant genetic component is implicated in handedness but little is known about the underlying molecular determinants. Recently we have identified the first genetic association with handedness at a genome-wide significance level (p < 5 × 10−7). The associated genetic markers lie within an intronic region of PCSK6, a gene known for its role in establishing left/right body asymmetries in early development and therefore a strong candidate for influencing handedness. Intriguingly, the association is specifically found in people with dyslexia.
The first aim of this project is to understand at a molecular level how genetic variation at the PCSK6 locus affects gene function. You will use different molecular biology techniques to study effects on gene expression and alternative splicing regulation, such as chromatin immuneprecipitation (ChIP) gene-reporter and gel-shift assays. Extensive use of bioinformatics and web-based resources will be employed to guide the experiments. The second aim is to elucidate the specificity of this association observed only in people with dyslexia. You will be part of a multidisciplinary team and will integrate your work with data from large genetic association studies and functional genomics resources. In particular you will be involved in evaluating the relevance of genexgene interactions and network pathways to explain phenotypic variation.
Key publications
Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Talcott JB, Stein J, and Monaco AP. (2011) PCSK6 is associated with handedness in individuals with dyslexia. Human Molecular Genetics, 20:608-614
Dennis MY, Paracchini S, Scerri TS, Prokunina-Olsson L, Knight JC, Wade-Martins R, Coggill P, Beck S, Green ED, and Monaco AP. (2009) A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene. PLoS Genetics, 5(3):e1000436.
Funding Notes
We are looking for an enthusiastic candidate who holds a first or upper-second class degree (or equivalent, e.g. MSc) in Biological Sciences, or a related subject from a recognised academic institution. Experience in molecular biology and an interest in human evolution will be an advantage.
This PhD studentship, starting no later than October 2012, is funded for three years (stipend and Home/EU fees).
This PhD studentship, starting no later than October 2012, is funded for three years (stipend and Home/EU fees).
