Objective
Intellectual disability (ID) is a neurodevelopmental disorder with a strong genetic component. For many patients the genetic cause is yet unknown as no protein-damaging mutations can be identified. To accurately predict the risk for ID from a person’s complete DNA sequence, it is essential to know how and when genetic perturbation of a gene regulatory element causes abnormal neurodevelopment. The knowledge and statistical methodology to do so are currently lacking.
Recently, the ENCODE and Roadmap Epigenomics projects identified millions of gene regulatory elements across a wide range of tissues. These regulatory elements are small DNA regions where cooperative binding of specific transcription factors (TFs) strongly influences the level of expression of one or more genes, often in a highly tissue-specific manner. However, since only static characterizations are available, it is very difficult to predict how the transcriptional network defined by the regulatory elements responds to genetic perturbations.
I will therefore perturb gene regulatory elements underlying ID by knocking-down the expression of established ID transcription factors in neurons. Previous efforts relied on partial or noisy measurements of TF binding. Instead, I will use TF-footprinting to obtain a complete view of how the knock-down perturbs TF-binding in gene regulatory elements. Combining this with gene expression and epigenetic profiling, I will model of how perturbation of cooperative binding in regulatory elements causes misregulation of ID and neurodevelopmental genes. To predict how perturbation of the transcriptional network disrupts biological pathways, I will integrate in my Bayesian network model existing data sets of neuronal morphology, structural brain imaging GWAS, and behavioural studies in model organisms.
My research will provide much-needed understanding and methodology to predict the functional consequences of genetic perturbation of gene regulatory elements for ID.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences neurobiology
- social sciences psychology behavioural psychology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics epigenetics
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
6525 XZ Nijmegen
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.