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  • Spain
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  • Posted on: 11 March 2025

DC9: Enhancing the activity of therapeutic ASO by genetic modulation and sequence motif adjuvants

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11 Mar 2025

Job Information

Organisation/Company
Universitat de Valencia
Research Field
Biological sciences » Biology
Medical sciences
Researcher Profile
First Stage Researcher (R1)
Positions
PhD Positions
Country
Spain
Application Deadline
Type of Contract
Temporary
Job Status
Full-time
Hours Per Week
35
Offer Starting Date
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
  • 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
     

Project description:

The aim is to overcome the known difficulties of therapeutic ASO to traverse endosomal bilayers, relating non-optimised cellular uptake and endosomal escape mechanisms, and access the nuclear/cytoplasmic compartments. These biological mechanisms are still poorly understood, but it is recognized that ASO activity may still be greatly improved. For this purpose, DC9 will screen for new means to favour it through (a) RNA interference by using cherry-picking siRNA libraries based on the literature (i.e., CADS, GTPase genes) and (b) the evaluation of 12-mer adjuvant sequences attached to the ASO, using a positional scanning method previously used by UVEG. DC9 will use HeLa cell lines containing stable fluorescent splicing reporter constructions and defined ASO known to target them. Quantification of intracellular activity will be done after non-forced internalization (gymnosis) of the oligos. Cell sorting by fluorescent levels (FACS) and cytometry analysis will identify combinations of “oligo+ manipulation” (gene silencing or sequence) providing a significantly different fluorescent signal ratio. Those manipulations promoting activity will move to (c) prioritization, by direct estimate of the amount of oligo internalization (ELISA), and (d) definition of mechanism of action for the improvement of the oligo activity observed. Finally, DC9 will (e) validate the results in DM1 disease by using oligos (antimiRs, gapmers, etc.) already in development by the Consortium (Universitat de Valencia, Inserm, Stichting Radboud Universitair Medisch Centrum), and involving patient hiPSC-derived cell models and transgenic DM1 mice (available at Centre d’Etudes des Cellules Souches and Inserm). DM1 hallmark features (expanded DMPK levels, RNA foci, splicing dysregulation, miRNA levels, muscle myotonia, and strength) will be evaluated.

Candidate’s Profile:

We are looking for a highly motivated and ambitious DC candidate with a solid background in genetics and cellular biology, particularly interested in the field of RNA and drug discovery. The ideal candidate should have a Master’s degree (or equivalent bachelor's degree) in Molecular Life Sciences, Physiology, Biomedical Sciences, or a related discipline, along with hands-on experience in gene and protein quantification, immunofluorescence, microscopy, and/or cell culture techniques and protocols. Previous experience with transcriptomics, proteomics, and disease models, both in vitro and in vivo, will be highly valued.  

The candidate will demonstrate excellent analytical and problem-solving abilities, critical thinking, and an independent yet collaborative research mindset. Intellectual curiosity, adaptability, and resilience in tackling scientific challenges are key assets. The candidate must have communication skills and a proactive attitude toward teamwork in a multidisciplinary and international research environment. Proficiency in English is essential, and basic knowledge of Spanish is recommended to facilitate broader institutional and social interactions. 

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

(1) Stichting Radboud Universitair Medisch Centrum, Derick Wansink (Nijmegen, The Netherlands). Characterisation of the mechanism of action for genes or motifs identified after the screening. (2) Centre d’Etudes des Cellules Souches, Sandrine Baghdoyan (Evry, France). Validation of enhancer delivery methods in DM1-iPS-derived cell model

Application Process

Interested candidates should submit a single PDF document to Arturo Lopez-Castel (Arturo.Lopez-Castel@uv.es) and recruitment.entrydm@gmail.com, named with your full name.

  1. 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.
  2. 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. 
  3. Copy of passport or National Identify Card.
  4. Copies of academic certificates (BSc, MSc, and any other relevant diplomas), translated into English, including expected final grade and date.
  5. Proof of English proficiency, demonstrated by IELTS, TOEFL, or a university certification confirming that the degree or MSc thesis was conducted in English.
  6. 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.

For more information about the project: https://www.institut-myologie.org/2025/02/10/entry-dm-un-reseau-europeen-pour-former-une-nouvelle-generation-de-jeunes-chercheurs-sur-la-dm1-entretien-avec-mario-gomes-pereira/

Where to apply

E-mail
Arturo.Lopez-Castel@uv.es

Requirements

Research Field
Biological sciences » Biology
Education Level
Master Degree or equivalent
Research Field
Medical sciences
Education Level
Master Degree or equivalent
Skills/Qualifications

Candidates must hold a Master’s degree (or equivalent) in biology, biomedicine, neuroscience, chemistry, bioengineering, or related fields. Exceptionally, the Universitat de València may admit highly qualified candidates with only a Bachelor’s degree from educational systems where a Master’s is not required for doctoral studies, provided their academic background meets the university’s admission criteria.

Languages
ENGLISH
Level
Excellent
Languages
SPANISH
Level
Basic
Research Field
Biological sciences » BiologyMedical sciences

Additional Information

Benefits
  • 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. Exceptionally, the Universitat de València may admit highly qualified candidates with only a Bachelor’s degree from educational systems where a Master’s is not required for doctoral studies, provided their academic background meets the university’s admission criteria. 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. 

Additional comments

UVEG will evaluate candidates without a master's degree individually to assess whether their academic background and coursework meet the university's standards.

Website for additional job details

Work Location(s)

Number of offers available
1
Company/Institute
Universitat de Valencia
Country
Spain
City
Valencia
Postal Code
46010
Street
Av. de Blasco Ibáñez, 13
Geofield

Contact

State/Province
Please Select
City
Valencia
Website
Street
Av. de Blasco Ibáñez, 13
Postal Code
46010
E-Mail
Arturo.Lopez-Castel@uv.es
recruitment.entrydm@gmail.com

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