DC2: The complexity of DM repeat expansions: new challenges in developing personalised molecula[...]

Organisation/Company: Università Degli Studi di Roma Tor Vergata

Department: Department of Biomedicine and Prevention

Research Field: Biological sciences, Medical sciences

Researcher Profile: First Stage Researcher (R1)

Positions: PhD Positions

Country: Italy

Application Deadline: 30 May 2025 - 12:30 (Europe/Paris)

Type of Contract: Temporary

Job Status: Full-time

Hours Per Week: 40

Offer Starting Date: 1 Sep 2025

Is the job funded through the EU Research Framework Programme? Horizon Europe - MSCA Marie Curie Grant Agreement Number 101169266

Is the Job related to staff position within a Research Infrastructure? No

Offer 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.

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.

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: (1) development of innovative disease models and exploring disease mechanisms, (2) optimising ASO-based therapies, and (3) 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.

To achieve these goals, ENTRY-DM has assembled a consortium of leading European research institutions and biotech companies, providing a truly international and intersectoral research environment. The 9 academic and 2 non-academic beneficiaries include renowned universities and research centres in France, Spain, Italy, the Netherlands, Germany, and Poland, complemented by 13 associated partners, including patient organisations and biotech companies. Each PhD candidate will be hosted in a dynamic, multi-disciplinary and international setting, benefiting from inter-sectoral secondments, world-class supervision, and specialised training in advanced research techniques, innovation, and career development.

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.

Beneficiaries & Research Institutions

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
• Radboud University Medical Centre (Nijmegen, The Netherlands) – 2 positions

Project Description:

The underlying mechanisms of genotype-phenotype correlation in DMs are still poorly known, especially for DM2 patients. Moreover, about 10% of DM1 patients carry CTG expansions interrupted by naturally occurring variant repeat (VR) motifs, which are considered major cismodifiers of molecular and phenotypic consequences. Heterogeneity across tissues, somatic instability, and the relative technical difficulty of measuring repeat length distributions using PCR-based methods currently hamper the possibility to establish and refine these crucial correlations. This project will exploit a diagnostic protocol based on a combination of NGS (developed by Genartis) and PCR-based methods enabling the full characterization of pure and interrupted DM expansions. DC2 will correlate the length, structure and methylation pattern of the DM loci with the molecular and clinical phenotype in a selected cohort of DM patients, to identify relevant genotype-phenotype correlations. Moreover, DC2 will produce cell lines overexpressing different motifs of C/CTG interruptions, as tools to study the molecular and functional impact of VRs on RNA foci dynamics, and develop personalized molecular therapeutic strategies.

Candidate’s profile:

We are looking for a highly motivated and skilled DC with a solid background in Medical Genetics and Cellular Biology to join our research project aimed to explore the structural, molecular, and functional aspects of expanded alleles in DM patients. The candidate should hold a Master's degree (or equivalent) in Genetics, Biology, Molecular Biology, Biomedicine, or a related field. A strong interest in genetic diseases and motivation to contribute to the development of therapeutic strategies for patients is essential. Prior experience in key molecular genetics techniques, including DNA/RNA extraction, PCR, RT-PCR, genotyping and NGS data analysis is required. Hands-on experience in cell culture and plasmids construction is highly desirable. The ideal candidate should demonstrate ability to plan and conduct experiments independently, analyse data, and draw conclusions.

Excellent communication and teamwork skills are necessary to work in an international and interdisciplinary context, including academic researchers and physicians. Proficiency in English is mandatory, and basic knowledge of Italian is highly recommended to enhance institutional and social interactions.

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

(1) Genartis, Marzia Rossato (Verona, Italy). Training in third generation DNA sequencing technologies and bioinformatic tools for the DNA-seq analysis of the DM1 and DM2 loci. (2) Stichting Radboud Universitair Medisch Centrum, Derick Wansink (Nijmegen, The Netherlands). Investigation of the effects of VRs on the molecular pathogenesis of DM1 by advanced RNA-FISH and IF staining techniques.

• 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.

• Cutting-edge research training in oligonucleotide-based therapies for rare diseases.
• First-hand experience in translational research, working across biology, chemistry, bioengineering, computational biology, and clinical research.
• International, interdisciplinary, and intersectoral mobility, with secondments across Europe and USA.
• Joint supervision by leading experts from academia, industry, and clinical sectors.
• Participation in international conferences, workshops, and transferable skills training.
• Competitive salary, mobility allowance, and family allowance (if applicable), following MSCA-DN funding rules.

Marie Sklodowska-Curie PhDs are paid a competitive gross salary of 3,400 €/month, adjusted for their host country, a Mobility Allowance of 600 €/month and, for researchers who have a family, a Family Allowance of 660 €/month. All amounts are subject to deductions and taxes. Family is defined as persons linked to the researcher by (a) marriage, or (b) a relationship with equivalent status to a marriage recognised by the national legislation of the country of the beneficiary or of nationality of the researcher, or (c) dependent children who are actually being maintained by the researcher.

Eligibility criteria

To apply for one of these PhD positions, the applicant must fulfil the following conditions at the day of recruitment:

• MSc degree. Candidates must hold a Master’s degree (or equivalent) in biology, biomedicine, neuroscience, chemistry, bioengineering, or related fields. Candidates must not have been awarded a previous PhD degree.
• Trans-national mobility: The applicant must have not resided in the country where the research training takes place for more than 12 months in the 3 years immediately prior to recruitment, and not have carried out their main activity (work, studies, etc.) in that country (MSCA mobility rule).
• English proficiency: Applicants must have excellent English proficiency, at least B2 level (written and spoken).

Selection process

Our selection procedure will adhere to the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers, to ensure global accessibility and a transparent, competitive selection process. The submissions will be first screened for eligibility, after which each supervising team will make selection decisions. Selection criteria will consider motivation, interests, academic qualifications, grades, and prior experience. The shortlisted candidates will be invited by the supervising team to meet virtually and/or visit the host institution. The final decision to offer a position will rest with the supervising team of each DC position. All candidates will be informed of the outcome of their applications.