PhD candidate gene-targeted treatment for ALS Utrecht • UMC Utrecht

ALS is a rapidly progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons. In 2024, after 150 years of research, the first effective gene-targeted therapies became available for patients with specific SOD1 gene mutations (<1% of all ALS patients).

The main objective of this PhD project is to develop gene-targeted therapies for newly identified ALS-associated genes. The doctoral candidate will acquire a broad set of skills, including trans-differentiation of fibroblasts into neurons (iNeurons), development and screening of antisense oligonucleotides (AONs), live-cell imaging, and transcriptomic analyses.

Laboratory work will involve optimizing protocols to convert patient-derived skin cells into neurons (iNeurons). New AONs will be screened through reporter assays and RNA sequencing in iNeurons. Using advanced techniques such as automated live-cell imaging, electrophysiology and biomarker analyses, effective AONs will be selected. Ultimately, the goal is to develop an AON that can be translated into a treatment for ALS patients.

The candidate will work closely with a multidisciplinary team consisting of colleagues from biomedical sciences, medicine, bioinformatics, and statistics, both within and outside UMC Utrecht (including the Dutch Center for RNA Therapeutics and Charles River Laboratories). Informal yet close collaboration with fellow PhD candidates, postdoctoral researchers, and technicians is expected.

The ALS Center in Utrecht is the primary center for ALS patients in the Netherlands and hosts the largest ALS research group in Europe. Genetic research at the center is conducted within an international collaborative network in which UMC Utrecht plays a leading role (). The focus lies on identifying genetic causes and risk factors for ALS, as well as genetic variations influencing disease progression.

There is broad expertise in genetic analyses, ranging from translational studies using iPSC-derived motor neurons to analyzing large genetic datasets with (hundreds of) thousands of patients and controls. We collaborate with the Department of Translational Neuroscience at UMC Utrecht’s stem cell facility. There are international collaborations with academic and pharmaceutical partners, allowing for (international) exchange projects.

An enthusiastic and eager-to-learn researcher with a completed Master's in biomedical sciences, neuroscience, molecular medicine, or comparable, with affinity for laboratory work, who wants to dedicate themselves to finding new treatments for ALS.

An enthusiastic and eager-to-learn researcher with a completed Master's in biomedical sciences, neuroscience, molecular medicine, or comparable, with affinity for laboratory work, who wants to dedicate themselves to finding new treatments for ALS.

• A salary between € 3108 - € 3939 gross per month (salary scale OIO), based on full-time employment (36 hours).
• Year-end bonus of 8.3% and holiday allowance of 8%.
  Pension insurance with ABP. We take care of approximately 70% of the monthly contribution.
• 100% public transport reimbursement. Are you coming on foot, by bike or by car? You will then receive a reimbursement of € 0.18 per km (by car up to a max. of 40 km one way).
• Possibilities to develop yourself personally and professionally.
• The option to select additional employment benefits in exchange for gross salary, such as purchasing a bicycle and memberships.