You will lead your own project to discover and characterize modifiers of disease pathways in iPSC models of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that effects 1 in 350 people. Your work will leverage markers of ALS pathology that have already been established using a combination of human genetics analyses, omics / neuropathological profiling of postmortem patient tissue and iPSC studies.

For the first phase of your project, you will implement a protocol to conduct FACS sorting of iPSC derived motor neurons based on key disease markers. You will then combine this protocol with a pooled genomewide CRISPR deletion screening platform that has already been optimized for mammalian cell culture systems. Through this, you will prioritize candidate modifiers of key ALS phenotypes. This prioritization process will also be informed by various technical validations, mechanistic hypotheses and by integrating your results with parallel genetic analyses of whole genome sequencing data from large numbers of ALS patients (in partnership with project collaborators).

In the second phase of your project, you will dissect the mechanistic links between prioritized modifiers and ALS phenotypes. Through this you aim to provide new insights into disease mechanisms and establish novel targets for ALS translational research. The tools available to you to perform this work include a range of established ALS iPSC lines, isogenic controls, iPSC neuron/organoid culture facilities, microfluidic systems, cellular imaging (calcium, confocal, lightsheet) as well as standard biochemistry and neurobiology techniques. A range of assays for specific ALS phenotypes have also already been established. Your work will also be supported by interactions with colleagues that have experience in ALS, iPSC models, bioinformatics, genomics and a diverse areas of neuroscience.

• You are an established postdoctoral researcher or recently graduated PhD in a relevant scientific discipline and demonstrable experience in molecular cloning and iPSC models.
• Strong preference is given to candidates with a neuroscience background.
• You are motivated to grow your career by taking ownership of a research project focused on molecular mechanisms in neurodegenerative disease.
• Prior experience in cell sorting, in situ hybridization assays, lentiviral transduction, CRISPR technologies or bioinformatics is valued but not required.
• You are interested to combine iPSC models of ALS with high throughput perturbation assays and subsequent functional studies.
• You are a team player, you enjoy collaboration across disciplines and you are a good communicator.

The maximum salary for this position (36 - 36 hours) is € 5.504,00 gross per month based on full-time employment.

In addition, we offer an annual benefit of 8.3%, holiday allowance, travel expenses and career opportunities. The terms of employment are in accordance with the Cao University Medical Centers (UMC).

The project will be performed within the department of Translational Neuroscience at the UMC Utrecht Brain Center. The department uses a wide range of cutting edge technologies, disease models and computational tools to study development and disease in neural systems. You will also work within the framework of the Dutch ALS centre (ALS centrum), a world leading multidisciplinary unit dedicated to advancing translational, preclinical and clinical research in ALS.

The project will be supervised by Prof Jeroen Pasterkamp and Dr Kevin Kenna. Your work will leverage state of the art facilities as well as multiple established collaborations within the UMC Utrecht.

Contact our colleague:
Marie Hagen
088 75 688 05
m.hagen-3@umcutrecht.nl