Vacancy PhD candidate 'Rescuing disrupted single-cell and neural networkactivities in human DM neural models using ASO (DC7)'

Job description

The ENTRY-DM Doctoral Network, funded under the prestigious Marie Skłodowska-Curie Actions – Doctoral Networks (MSCA-DN) programme, is offering 14 fully funded PhD positions across leading European institutions. Join ENTRY-DM and contribute to the next wave of RNA-based therapeutics for myotonic dystrophy, a field at the cutting edge of precision medicine and molecular therapies. Be part of a transformative research network that will shape the future of rare disease treatment.

Myotonic dystrophy (DM) is the most common inherited muscular dystrophy in adults. It is a complex multi-systemic disorder, impacting not only skeletal and cardiac muscle but also the nervous system, among others. Despite recent advances in understanding the genetic and molecular mechanisms of DM, no effective treatment is currently available. The use of antisense oligonucleotides (ASOs) to counteract the disease-causing mutant RNA has faced delivery challenges and insufficient therapeutic efficacy. The development of clinically viable RNA-targeted therapeutics requires overcoming key scientific and technological hurdles, including poor ASO biodistribution, limited penetration of critical tissues, and the lack of reliable biomarkers to monitor disease progression and treatment response.

ENTRY-DM aims to transform the therapeutic landscape for DM by training a new generation of creative PhD researchers in a structured, interdisciplinary research programme.

The project will focus on three major research objectives:

• Development of innovative disease models and exploring disease mechanisms.
• Optimising ASO-based therapies.
• Defining clinical biomarkers for clinical trials.

PhD researchers will investigate genotype-phenotype correlations and RNA dynamics, leveraging cutting-edge genomics, bioinformatics, stem cell research, bioengineering of innovative 3D disease models, medicine chemistry, advanced imaging techniques, as well as neuropsychology approaches and clinical applications, in a truly multidisciplinary project.

Projectdiscription
The goal of this project is to develop patient-specific neural models studying the neuropathological processes affected by DM1- and DM2-related repeat expansions. DC7 will use established robust protocols for differentiation of patient hiPSCs to neural lineages, including excitatory cortical neurons, inhibitory neurons and astrocytes. As control for further experiments, DC7 will use iPSCs from healthy individuals and also generate isogenic hiPSCs from DM1-patient lines in which the repeat has been removed by a dual CRISPR/Cas9-NHEJ protocol. DC7 will use the established neural models for functional evaluation of the efficacy of ASO and antagomirs.

To this end, DC7 will conduct extensive analyses of the differentiated iNeurons and astrocytes following therapeutic intervention. These will include morphological analysis, cell intrinsic properties, neural network activity and parameters associated and brain cell phenotypes, such as the number of foci, alternative splicing. iNeurons co-cultured with astrocytes on microelectrode arrays (MEA) will be used to non-invasively measure spontaneous neural network activity before and after treatment.

RUMC has benchmarked the robustness and sensitivity of MEA-derived neuronal activity patterns for multiple different neurodevelopmental disorders. DC7 will combine the MEA measurements with RNA sequencing (MEA-seq) to identify deregulated expression and splicing of genes to identify mechanisms that are relevant to DM-neuropathology and rescued by therapeutic strategies.

Place of work

The ENTRY-DM consortium includes 9 academic and 2 non-academic beneficiaries from 6 European countries, along with leading associated partners from academia, industry, and patient organisations. PhD positions are available at the following institutions:

• Inserm (Paris, France) – 2 positions.
• Universitat de València (Valencia, Spain) – 2 positions.
• Institut de Bioenginyeria de Catalunya (Barcelona, Spain) – 1 position.
• Università di Roma Tor Vergata (Rome, Italy) – 1 position.
• Radboud University Medical Centre (Nijmegen, The Netherlands) – 2 positions.
• Ludwig-Maximilians-Universität München (Munich, Germany) – 1 position.
• Adam Mickiewicz University in Poznań (Poznan, Poland) – 1 position.
• Centre d’Etudes des Cellules Souches (Evry, France) – 1 position.
• Genartis (Genova, Italy) – 1 position.
• Université Paris Cité (Paris, France) – 1 position.
• Consejo Superior de Investigaciones Científicas (Barcelona, Spain) – 1 position.

ENTRY-DM is an ambitious interdisciplinary and intersectoral training programme that will equip the next generation of researchers with the expertise to develop novel oligonucleotide-based therapies for myotonic dystrophy. This programme brings together leading academic institutions, innovative biotech companies, and patient advocacy groups, forming a unique collaborative environment for doctoral training at the intersection of fundamental science, translational medicine, and clinical application.

Radboudumc
Welcome to Radboud university medical center (Radboudumc), where scientific breakthroughs are born through the curiosity and passion of our collaborating researchers in a vibrant environment. We believe trust and excitement are crucial elements to achieving our goals, and we approach our research as teams and with the utmost rigor to make a significant impact on health and healthcare. Our researchers are driven by their fascination with the biological, psychological, and sociological mechanisms underlying health and healthcare. They collaborate with partners from all over the world to improve health outcomes for all. Radboudumc unites patient care, research, education, and corporate learning, which allows us to approach our mission to shape the health and healthcare of the future in an innovative and person-centered way.

Our ambition is to lead the way in the pursuit of prevention, sustainability, meaningful care. We believe that through our research, we can significantly improve the health and well-being of society. Join us on our mission to make a difference in healthcare. Become a part of our community of gifted researchers, professionals or patient partners who are dedicated to making a real impact on population health and healthcare. 

Read what it is like to do a PhD at the Radboud University Medical Center.

Profile

We are looking for a motivated and ambitious PhD candidate with a strong interest in stem cell biology, molecular biology, and neurobiology. The ideal candidate will have a passion for molecular and cellular techniques, cell culture, and neurophysiology. An MSc degree (or equivalent) in molecular life sciences or a related field is required, along with practical experience in molecular and cellular techniques, including work with IPSCs and IPSC-derived neural cells.

Candidates with strong intrinsic motivation and initiative are highly valued. An accurate working attitude and excellent analytical and problem-solving skills, as well as a commitment to advancing research, are essential. Effective communication and teamwork abilities are crucial for collaboration within our group. Proficiency in English is mandatory; knowledge of or willingness to learn Dutch is a plus.

Responsibilities include developing and standardizing iPSC-based cell models and analysis of their effect on neural network properties as well as single cell neurophysiological properties. Other envisaged studies include transcriptomic analyses and investigation of the effect of ASOs and small molecules.

You will write scientific publications, resulting in a thesis. You will present this research at local, national, and international meetings, work collaboratively with other PhD candidates and scientists, and engage in research in a stimulating environment, including travel to other institutes.

Doctoral candidates will spend time on secondment during their 36 month employment contracts. Anticipated secondments for this position are:

• Virginia Commonwealth University Health, Nicholas Johnson (Richmond, USA). Develop  skills in analysis of RNA splicing alterations.
• Sanofi, Ricardo Mondragon-Gonzalez. Training in design on modulators of ASO and initial analysis of efficacy.

Employment conditions

Starting date is 1 September 2025. At Radboud university medical center, you build on your future. We are committed to providing the best care, education, and research. And we are true to our word, because we help you develop and seize opportunities and give you the room to grow. As an employer, we believe that employees should feel vital and happy at work in all stages of life. We are also committed to creating a healthy and safe working environment. Our employment conditions contribute to that. What we offer:

• Upon commencement of employment, you will start at scale 10A, step 0 (€ 3.017 based on a full-time appointment). Over a maximum period of 4 years, you will progress to scale 10A, step 3 (€3.824 based on a full-time appointment). You will also receive an 8% holiday allowance, an 8.3% end-of-year bonus, and a 47% to 72% bonus for working unsocial hours.
• From 1 July 2025 an increase in salary with 3%.
• 176 vacation hours per year based on a 36-hour working week. 

And there is more..

• An Employment Conditions Selection Model, allowing you to use part of your employment conditions to your choosing. For example, you can use your gross salary to purchase additional vacation hours or hours for providing informal caregiving. Or, for example, you can use your gross end-of-year bonus to purchase a bicycle, so you pay less tax.
• Plenty of opportunities for personal development. You can take a variety of courses in our online learning environment. 
• Your well-being and vitality are a priority. For example:
  • Save time for work-life balance leave. 
  • You can enjoy unlimited access to a variety of activities five days a month and take advantage of all the facilities at Radboud Sport & Culture for only €27.05 per month (instead of €41)
  • Healthy Professionals program to help you manage your energy. 
  • Company Support Team and a personal coach if you are going through a life-changing event.
  • Financially beneficial working less through a Generation Scheme as you approach state pension age.
• Support in achieving a good work-life balance at every stage of your life. Examples:
  • Advice and courses on, for example, 'Millennial dilemmas' and 'Your Career After 57'.
  • Activities at our own mindfulness center.
  • Informal caregiving consultations if you have questions about juggling work and caregiving responsibilities at home.
• In addition to statutory pregnancy and maternity leave, Radboud university medical center offers 26 weeks of parental leave, nine of which are paid. In addition, as a partner you can take a maximum of five weeks of supplementary partner leave. During supplementary partner leave and parental leave, we supplement the UWV benefit up to 100% of your salary.
• Pension accrual at the ABP Pension Fund. Radboud university medical center pays 70% of the pension premium. 
• Discounts on supplementary packages of two group health insurances and ten other types of insurance, from home insurance to legal assistance.
• An allowance for your commuting costs of € 0.18 per km up to a maximum of 40 km one way. If you use public transport to commute, we will fully reimburse the public transport costs (2nd class). If you regularly work from home, you will receive a working from home allowance of € 2.40 per day.

 

Application procedure

Are you ready to think further for our patients and our care? We would like to receive your application before 2 June 2025. We will then contact you shortly. In the Application procedure you will find all the requirements for this application. Applications failing to include the requested documentation, who do not indicate the preferred projects or do not meet the eligibility criteria, will not be considered.

Good to know

• This position requires a Certificate of Conduct (VOG).
• You can find more information about our application procedure and frequently asked questions on our website.
• Will you be our new colleague? Then you will be given the time and space to get to know your role, your workplace, and your colleagues. An induction day for all new colleagues is an integral part of your onboarding program. 

We are recruiting for this position ourselves. Unsolicited marketing is not appreciated, but do feel free to share the vacancy in your network!

Contact

Any questions? Or wondering what it is like to work at Radboudumc? Then email to Hans van Bokhoven, Professor. Use the Apply button to submit your application. 

Application procedure
Interested candidates should upload:

• A detailed CV (maximum two pages), specifying educational background (name of university/universities, year degree(s) obtained, title(s) of degree(s)), qualifications, work experience, skills, research interests, list of publications (if any) and the names and contact details of two referees.
• A motivation letter (maximum two pages), describing the candidate’s interest in the network, previous research experience, and current research interest outlining the fit to the desired PhD Project.
• If you are planning to apply to more than one position in the network, please limit your applications to three positions maximum (from DC1 to DC14) and please provide a separate document detailing which positions you have applied for.
• Copy of passport or National Identify Card.
• Copies of academic certificates (BSc, MSc, and any other relevant diplomas), translated into English, including expected final grade and date. Proof of English proficiency, demonstrated by IELTS, TOEFL, or a university certification confirming that the degree or MSc thesis was conducted in English.
• Two recommendation letters (maximum 1 page each). Only documents in English will be accepted.

Applications failing to include the requested documentation, who do not indicate the preferred projects or do not meet the eligibility criteria, will not be considered.