We are recruiting for an exceptional individual to join as a Postdoctoral Researcher in the laboratory of Dr Arpan Mehta. This is a fixed-term appointment for 18 months, with potential extension at the end of the term.

We are recruiting for a driven individual to join the laboratory of Dr Arpan Mehta, a clinician-scientist, with expertise in cell biology and/or gene-editing to conduct an innovative pooled CRISPR screen in human motor neurons derived from induced pluripotent stem cells. The overarching goal of the lab is to undertake fundamental research to understand the molecular basis of amyotrophic lateral sclerosis (ALS), a form of motor neuron disease (MND), through open and interdisciplinary collaborations within and outwith of our unit.

The successful applicant will undertake a project as part of the MND Accelerator (MNDAcc) initiative funded by the Medical Research Council and National Institute for Health and Care Research to make the translation of discoveries into therapeutics easier for motor neuron disease and frontotemporal dementia. The goal is to make robust discoveries and share data openly in the space of 18 months.

The project will investigate mechanisms of the C9ORF72 repeat expansion mutation, the commonest genetic cause of ALS. The applicant will undertake CRISPR/Cas9 screening of C9ORF72 patient-derived motor neurons (MNs) in the presence of glutamate excitotoxicity, and microglial inflammatory stressors induced by C9ORF72 microglia, to identify candidate target protein kinases that regulate the survival of MNs.

The successful candidate would also benefit from career mentorship from other PIs in the Unit including, Professor Sir Philip Cohen FRS and Professor Dario Alessi FRS (Unit Director) to help advance their careers. The project is ambitious and innovative, and will be in collaboration with Dr Wenting Guo at NeuroStra, Strasbourg, France, offering opportunities for international networking, too. The candidate would be put forward for prizes as appropriate, and receive exposure to patient and public engagement and involvement, through Dr Mehta’s parallel role as a practising neurologist.

Overall, this position provides an exciting opportunity to be involved in world-class research projects and for the successful applicant to carve themselves a major international reputation. The successful candidate will have an opportunity to be trained in a suite of state-of-the-art techniques during the project.

Your priorities will include:

• Build C9ORF72-iCas9 iPS cell line and perform quality control followed by differentiation to motor neurons and microglia using published protocols.
• Optimise and perform a kinome-wide CRSIPR/Cas9 knock out-screen and sgRNA enrichment analysis.
• Validate the top candidate hits and create a CROP-seq library in partnership with UK Dementia Research Institute (UK DRI) single-cell facility.
• Public and patient involvement and engagement presentations.
• Dissemination of protocols and data openly and through formal peer-reviewed publications.
• Advising and mentoring undergraduate and PhD students.

Candidate requirements:

• PhD in molecular biology with a track record of academic success.
• Highly organised, motivated and meticulous, with an ability to work independently and to drive a project forwards robustly and at pace.
• Expertise in iPS cell culture is highly desirable, although the successful candidate would be supported and trained (if necessary) by Dr Lindsay Davidson who leads our iPSC core facility.
• Prior experience in gene editing and CRISPR screens would be highly desirable.

Relevant publications:

Mehta AR, Gregory JM, Dando O, Carter RN, Burr K, Nanda J, Story D, McDade K, Smith C, Morton NM, Mahad DJ, Hardingham GE, Chandran S, Selvaraj BT. Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis. Acta Neuropathol. 2021 PMID: 33398403.

Banerjee P, Mehta AR, Nirujogi RS, Cooper J, James OG, Nanda J, Longden J, Burr K, McDade K, Salzinger A, Paza E, Newton J, Story D, Pal S, Smith C, Alessi DR, Selvaraj BT, Priller J, Chandran S. Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72-ALS iPSC-derived microglia contributes to neurodegeneration. Sci Adv. 2023 PMID: 37083530.

Mehta AR, Chandran S, Selvaraj BT. Assessment of Mitochondrial Trafficking as a Surrogate for Fast Axonal Transport in Human Induced Pluripotent Stem Cell-Derived Spinal Motor Neurons. Methods Mol Biol. 2022 PMID: 35412284.

Guo W, Wang H, Kumar Tharkeshwar A, Couthouis J, Braems E, Masrori P, Van Schoor E, Fan Y, Ahuja K, Moisse M, Jacquemyn M, Furtado Madeiro da Costa R, Gajjar M, Balusu S, Tricot T, Fumagalli L, Hersmus N, Janky R, Impens F, Vanden Berghe P, Ho R, Thal DR, Vandenberghe R, Hegde ML, Chandran S, De Strooper B, Daelemans D, Van Damme P, Van Den Bosch L, Verfaillie C. CRISPR/Cas9 screen in human iPSC-derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity. Alzheimers Dement. 2023 PMID: 35993441.

For further information about this position please contact Dr Arpan Mehta at amehta001@dundee.ac.uk.