Published | Deadline | Location |
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today | 13 Nov | Rotterdam |
Job description
Are you interested in the non-coding genome and how alterations of it can cause human disease? Are you interested in neurodevelopment and brain diseases such as epileptic encephalopathies? Would you like to work in a highly dynamic environment between the interphase of fundamental science and applied human clinical genetics, directly benefiting patients? And all of that in a fun, young and international team at a top university? Then join our expanding research team as a computational postdoc!
The current position is funded by a ZonMw Vidi project, which aims to solve missing heritability in epileptic encephalopathies. These are severely devastating disorders that present with intractable epileptic seizures at early age, severely affecting brain development of affected individuals and thereby imposing a large burden on patients, their families and the health care system. Many epileptic encephalopathies are caused by mutations in a large number of coding genes, but still around 50% of patients cannot be genetically diagnosed despite the high suspicion that it must be a genetic disorder. We hypothesis that some of this “missing heritability” is caused by genetic alterations in the non-coding genome, which contains important gene regulatory elements, such as enhancers. Our previous work, using computational analysis and massively parallel reporter assays has resulted in an atlas of such regulatory elements, of which we find many to regulate medically relevant human genes. In this project, we will explore how mutations in these regulatory elements might cause epileptic encephalopathy and other neurodevelopmental disorders. For this we will use analysis of patient whole genome sequencing data (both from our local patient cohort, our large network of international collaborators as well as from the Genomics England 100,000 Genomes Project), patient derived RNA-seq data, and data obtained in the wet-lab including massively parallel reporter assays, single cell analysis and chromatin conformation capture analysis in various cell models including brain organoids and zebrafish, combined with computational approaches including machine learning. Tight interplay with the wet-lab will allow functional validation of the various obtained findings, and close links to clinic and diagnostics will ensure immediate translation of findings to improve patient care.
Specifications
Erasmus MC (University Medical Center Rotterdam)
Requirements
Conditions of employment
Employer
Erasmus MC
You will be part of a highly international working environment in an inspiring, dynamic and productive team at the Barakat lab at the Clinical Genetics department of Erasmus MC, with access to a broad range of high-throughput next generation sequencing data, both from wet lab experiments as well as patient samples (https://www.erasmusmc.nl/en/research/groups/barakat-lab-non-coding-genome-in-clinical-genetics ).
The Barakat lab was established in 2017 at Erasmus MC, and focusses on deciphering molecular mechanisms leading to neurodevelopmental disorders, with a particular interest in the role of the non-coding genome. Using functional-genomics and computational approaches we aim to understand the gene-regulatory-landscape in cells representing neurodevelopment. Our long-term goal is to translate our research findings to the clinic, where we aim to develop novel diagnostics and therapies focusing on the so far, so often, neglected non-coding regions of the human genome. Next to our interest in fundamental gene-regulation, we apply disease-modelling for neurodevelopmental disorders using genome-engineering, induced pluripotent stem-cells, brain-organoids, and zebrafish. Our group, currently consisting of 10 members, is strongly embedded in the department, and forms an important bridge between research and clinic, ultimately leading to advancements for patients. Since 2017, we have published 33 papers (majority in top-10 journals) describing new disease entities and mechanisms, have obtained > 3 million euro funding (including competitive grants from CURE Epilepsy, EpilepsieNL, ZonMw Veni, ZonMw Vidi) and have been awarded a number of prizes, including an KNAW Early Career Award 2021.
Full publication record of the PI (incl. previous publications in Cell, Nature and Cell Stem Cell) can be found here:
https://orcid.org/0000-0003-1231-1562 https://pubmed.ncbi.nlm.nih.gov/?term=tahsin%20stefan%20barakat&sort=date&page=3
Additional information
For more information about this position, please mail Dr. Stefan Barakat, Principal Investigator t.barakat@erasmusmc.nl
In case of other requirements to apply:
Your application should include: motivation letter, Curriculum Vitae, list of courses and obtained grades during BSc, MSc and PhD program, a publication list, and a minimum of two reference letters.
If you are excited by the thought of this position and would like to apply, please do so by using the application form on our website.
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Application procedure
For more information about this position, please mail Dr. Stefan Barakat, Principal Investigator t.barakat@erasmusmc.nl
In case of other requirements to apply:
Your application should include: motivation letter, Curriculum Vitae, list of courses and obtained grades during BSc, MSc and PhD program, a publication list, and a minimum of two reference letters.
If you are excited by the thought of this position and would like to apply, please do so by using the application form on our website.
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