Nucleotide homeostasis and mitochondrial function: physiological and therapeutic implications
VHIR is seeking an outstanding and highly motivated postdoctoral researcher to apply for a Marie Sklodowska-Curie Postdoctoral Fellowship and join the Neuromuscular and Mitochondrial Disorders Research Group.
Marie Skłodowska-Curie Actions – Postdoctoral Fellowships (MSCA-PF)
The Marie Skłodowska-Curie Postdoctoral Fellowships (MSCA-PF) are part of the Horizon Europe programme and support postdoctoral researchers in developing an original research and innovation project through international mobility.
The programme aims to strengthen researchers’ careers through excellent science, international collaboration and interdisciplinary experience, while fostering integration in both academic and non-academic environments. The MSCA-PF call is highly competitive and represents an excellent opportunity to attract international talent and support researchers in consolidating their scientific careers through an ambitious mobility-based fellowship.
The 2026 call closes on 09/09/2026 (17:00 Brussels time). For candidates applying to a European Postdoctoral Fellowship, the fellowship duration is from 12 to 24 months
Full eligibility details: MSCA Postdoctoral Fellowships 2026
Background
Mitochondrial DNA (mtDNA) depletion/deletions syndromes (MDDS) are severe conditions caused by mutations in nuclear genes involved in mtDNA replication. dNTP imbalances are often associated to these disorders, either because the primary gene is involved in dNTP anabolic or catabolic pathways, or because the mtDNA aberrations secondarily alter dNTP metabolism.
The dNTP homeostasis is a therapeutic target for some MDDS For instance, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by the toxic accumulation of thymidine and deoxyuridine, and the treatments of this disorder aim to clear the overload of these metabolites. Also, the recent approval of thymidine and deoxycytidine to treat TK2 deficiency (Kigevvy™) constitutes the first therapy that changes the natural history of an MDDS form, extending the life expectancy of patients that otherwise would die in months or few years.
Preclinical studies support the notion that stimulating mtDNA replication by enhancing dNTP synthesis may be an effective treatment of other MDDS forms Moreover, our recent demonstration of dGTP binding the OXPHOS complex I constitutes a novel finding with potential unexplored functional consequences Therefore, the mitochondrial dNTP metabolism and how it is linked to the OXPHOS function and the mitochondrial disorders is currently a hot topic. Improving our knowledge in this field may result in therapies for devastating disorders with no effective treatment so far.
Objective
The general objective of this action is to investigate so far unexplored aspects of the dNTP metabolism in the context of the mitochondrial (dys)function, with especial focus on mtDNA replication and maintenance, including the investigation and further development of potential therapies for mtDNA maintenance disorders.
Examples of some specific objectives:
To identify genetic/protein/metabolic factors determining mitochondrial dNTP homeostasis and their relation with normal and dysfunctional mtDNA replication.
To study dNTP homeostasis in several in vitro and in vivo models of mtDNA replication defects, and to design/test therapy strategies to modulate dNTP imbalances.
To explore novel potential dNTP-related therapy targets, such as nucleoside/nucleotide transport or enzyme activation/inhibition.
To contribute to preclinical/clinical development of ongoing therapies, such as AAV-based gene therapy for MNGIE and other dNTP-related therapies in their track to the regulatory approval.
Beyond these examples, the details of the project will be finally re-designed according to the expertise of the candidate and will be jointly re-shaped once he/she is integrated in the research group.
Our Group
The research group of neuromuscular and mitochondrial disorders focuses its research activity on studying the pathophysiological mechanisms of mitochondrial diseases, especially those associated with defects in mtDNA maintenance. In addition, we have some research lines dedicated to the study of another group of metabolic disorders, the muscle glycogenosis. Some of our current research lines are:
Study of the pathomechanisms of MDDS and development of therapeutic strategies for them.
Pathophysiology of mitochondrial diseases due to defects in mitochondrial translation.
AAV-based gene therapy (for MNGIE disease and for mutations in GFM1).
Pathomechanisms of the McArdle's disease using a murine model of this disorder.
Coordination of EUROMAC (European registry of patients with McArdle's disease and other glycogenosis).
Work with cellular and mouse models (available mouse strains genetically modified in the following genes: Polg, Tk2, Dguok, Opa1, Tymp/Upp1, Ndufa10, Pygm).
The methodology will comprise, among other techniques, general molecular biology methods, real-time qPCR, digital PCR, enzymology-linked methods, dNTP assessment, targeted metabolomics (HPLC-mass spectrometry).
In addition, the VHIR core facilities offer well-equipped platforms: genomics, molecular diagnosis, cytometry, microscopy.
Applicants must hold a PhD degree or have successfully defended their thesis before the call deadline (09/09/2026)
Applicants must comply with the mobility rule, meaning they must not have resided or carried out their main activity (work/studies) in the host country for more than 12 months during the 36 months prior to the call deadline.
Basic communication skills in English
Official certificate to conduct experimental tasks with mice
Applicants must have a maximum of 8 years of postdoctoral research experience by the call deadline. This means candidates are generally eligible if they obtained their PhD on or after 10/09/2018 (possible extensions may apply, e.g. parental leave or long-term illness).
General laboratory biochemical and molecular biology methods
Any additional skills in the field of biomedical research methodology will be valuable.
Deadline to apply: 31-07-2026
VHIR embraces Equality and Diversity. As reflected in our values we work toward ensuring inclusion and equal opportunity in recruitment, hiring, training, and management for all staff within the organisation, regardless of gender, civil status, family status, sexual orientation, gender identity and expression, religion, age, functional diversity or ethnicity.
Information on Personal Data Protection:
Data Controller: Fundació Hospital Universitari Vall d’Hebron Institut de Recerca -VHIR-. Purpose: Personnel selection. Legal Basis: Your consent. Data retention period: One year. If you are selected, as long as the employment relationship is in force and legal responsibilities may arise. Data sharing: Does not occur, except for communications necessary to fulfill the purpose and those required by law to public and private bodies. Rights: You can access, rectify, delete, object to, and limit the processing of data, as well as request data portability where applicable, by contacting lopd@vhir.org DPO: dpd@ticsalutsocial.cat More information can be found here
Data Protection Authority: APDCAT
We are a public sector institution that promotes and develops the biomedical research, innovation and teaching at Vall d'Hebron University Hospital, the hospital of Barcelona and the largest of Catalan Institute of Health (ICS). The members of our Board of Trustees are the Catalan Ministry of Health, the Catalan Ministry of Economy and Knowledge (we are a CERCA center), Vall d'Hebron University Hospital, Bank of blood and tissues, the Autonomous University of Barcelona (UAB), of which we are an accredited research institute, and the Vall d'Hebron Institute of Oncology (VHIO), which together with VHIR is part of Accredited Institute of Campus Vall d’Hebron Institute by the Institute of Health Carlos III (ISCIII).
Since its creation in 1994, VHIR works to find solutions to the health problems of society, and contribute to spread them around the world. In more than 20 years we have achieved leadership in biomedical research at hospitals in our country, and we want to be recognised in 2020 as an excellent and competitive European Institute leader in clinical and traslational research linked to a university hospital.
In our institute are working more than 1,300 people, of which over 1,200 doing research and others, around 100, help to do it or transfer it to the society once made, whether in the form of projects, technology transfer and innovation, communication or fundraising, among others.
The best of our institution and its research staff is doing research to solve people’s health problems. Our task is not only basic or translational, we are leaders in clinical research. We have the beds of the hospital separated in less than 50 meters of laboratories and our patients will benefit from our research. In this we believe, and our efforts are focused on it. This is understood by industry leaders who are committed to our hospital, making it a world reference for its first clinical trials.
