About the project
3-year funded PhD – Developing targeted epigenetic strategies for Ribosomopathies
Part of EpiCrossBorders: International Helmholtz-Edinburgh Research School for Epigenetics (contact The School Office at [Email Address Removed])
This is an exciting PhD opportunity to join a well-funded collaborative PhD project. This project is a collaboration between leading research groups based at the Helmholtz Center Munich and the University of Edinburgh. The main part of the project takes place in the lab of Dr. Stefan Stricker at the Helmholtz Center Munich, but will include an exchange stay in the lab of Prof. Dr. David Tollervey at the University of Edinburgh.
Project description: Developing targeted epigenetic strategies for Ribosomopathies
Ribosomopathies are a group of congenital human diseases, which are caused by attenuated generation or activity of ribosomes. Patients’ cells possess reduced overall protein translation rates, ultimately resulting in complex pathologies.
We have developed several CRISPR based strategies enabling us to manipulate chromatin and gene expression at will. In a recently developed epigenome editing approach (TAPIR) we show that we can apply these tools to manipulate protein translation rates in mouse cell culture and living animals (Wiesbeck et al., in preparation). In this way, we have been able to prove that stem cell behavior during development is controlled by protein translation rates directly. Currently, we are investigating in detail, which chromatin mechanisms are causally involved in this process.
The suggested project will be conducted in collaboration with David Tollervey (Wellcome Centre for Cell Biology) and consists of two sub-projects. (1) We will apply TAPIR to a mouse model of ribosomopathy, recently established in the Tollervey lab (Robertson et al., 2021). (2) We will transfer, what we have learned from mouse cells and tissues to primary cells derived from ribosomopathy patients (and engineered iPSCs with patient mutations, available in the Tollervey lab). Since epigenome editing depends primarily on the targeting of dCas9 fusion proteins on gene regulatory elements, whose sequences are poorly conserved between species, the project will involve design of gRNA sequences and verification of their functionality. Other important aspects of the project are the adoption of in and ex vivo approaches and human iPSC culture. Taken together, this project will allow to comprehensively test, whether non-genetic CRISPR approaches are a suitable strategy to attenuate the effects of the ribosomopathy mutations.
More information and to apply:
All applications should go through our application portal, which you can find here: https://bit.ly/2WAG2Dx
Funding details: a three-year Doctoral contract and no tuition fees.
Eligibility: Applicants should hold a University Master’s degree (MSc or equivalent) to apply. with a strong background in biological sciences, (bio)chemistry, biomedicine computer science or related discipline, have excellent English language skills and a strong interest in an international PhD program. Your MSc degree has to include a Master Thesis on a scientific project.
Applicants still studying for their Master's degree may provide a provisional certificate or bona fide statement from the University stating the marks already obtained and estimated graduation date. Applicants accepted in the program are required to have completed their Master's degree before they can start their PhD work in the program. Applicants accepted within the program have to start their PhD work latest in fall 2022.
Applicants who wish to apply with a four-year BSc degree (equivalent to 240 ECTS) without a MSc, please contact the research School directly.
For more information and to apply please visit our website (https://www.helmholtzresearchschool-epigenetics.org).
Enquiries can be made by email ([Email Address Removed])
Deadline for applications: 15th October 2021
Start date: 1st October 2022
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