MSCA Doctoral Network -DECODES: Deciphering the Splicing Code in Human Disease
Alternative splicing (AS) is a fundamental post-transcriptional mechanism that enables a single gene to generate multiple protein isoforms, dramatically expanding proteomic diversity. Dysregulation of AS is now recognised as a hallmark of human disease, contributing directly to cancer progression, neurodegeneration, metabolic syndromes, and numerous rare genetic disorders. Despite major technological advances, the translation of AS biology into clinical benefit remains limited by critical gaps in mechanistic understanding and by the absence of an integrated framework capable of driving discoveries from molecular insight to therapeutic intervention.
DECODES, coordinated by the University of Santiago de Compostela, has been conceived to meet this challenge. It unites leading European scientists with highly complementary expertise to establish a coherent, interdisciplinary, and intersectoral research programme that bridges fundamental RNA biology with clinical and industrial translation. At its core, DECODES is a high-level doctoral programme that will provide advanced, multidisciplinary training spanning computational genomics, structural biology, disease modelling, RNA biochemistry, medicinal chemistry and pharmacological screening.
Embedded in a fully international, interdisciplinary and intersectoral environment, the programme will equip 15 Doctoral Candidates with state-of-the-art research expertise, comprehensive transferable skills and entrepreneurial competencies through structured coursework and immersive industrial secondments.
By integrating these diverse disciplines into a unified pipeline for the discovery of pathogenic isoforms and the development of precision splicing-targeted therapies, DECODES will push the boundaries of RNA splicing research and train a new generation of scientists uniquely prepared to become future leaders in academia, biotechnology and translational medicine.
A total of 15 PhD positions are available across all participating institutions. Please see the attached Word documents for further information on the available positions, where 4 of the offers will be located at CiMUS - USC. Check here for these individual projects:
- DC7 @University of Santiago de Compostela (Spain) - Prof. Marta Varela Rey
Discovery and functional characterization of the splicing signature during hepatic fibrosis development: The general aim is to uncover how splicing factors and alternative splicing events regulate the TGF-β–induced activation of hepatic stellate cells (HSCs) and contribute to liver fibrosis, with the goal of identifying new therapeutic strategies: (i) Define the role of alternative splicing in the TGF-β profibrogenic response. (ii) Identify and functionally characterise relevant splice variants and RNA-binding proteins. (iii) Evaluate targeted splicing modulation as a strategy to restore healthy HSC function.
- DC8 @University of Santiago de Compostela (Spain) - Prof. Ashwin Woodhoo
Molecular and Functional Analysis of Splicing Regulation in Demyelinating Nerve Disorders: The general aim is to uncover the molecular and functional role of AS in PNS demyelinating disorders: (i) Identify and characterize splicing events and RBPs that drive Schwann cell responses to injury and neuropathies (ii) Dissect molecular function of disease-relevant splice variants and RBPs. (iii) Assess whether targeted splicing modulation can prevent or reverse Schwann cell demyelination in disease models..
- DC12 @University of Santiago de Compostela (Spain) - Prof. Ashwin Woodhoo
Dissecting the biological and molecular function of ZFHX4 in Malignant Peripheral Nerve Sheath Tumors (MPNST): Preliminary data shows that ZFHX4 is a key driver of MPNST pathogenesis. The DC will (i) Dissect the biological role of the RBP ZFHX4 in MPNST pathogenesis. (ii) Define the functional impact of ZFHX4 on alternative splicing programs and isoform dynamics in MPNSTs. (iii) Elucidate, at atomic resolution, the structural and mechanistic principles governing ZFHX4 recognition of its RNA targets and its regulation of their splicing.
- DC15 @University of Santiago de Compostela (Spain) - Prof. Maria Isabel Loza García
Pharmacological Disruption of LSM2-8–Dependent Splicing in Malignant Peripheral Nerve Sheath Tumors: In preliminary studies, the LSM5 protein—an essential component of the LSM2–8 complex required for spliceosome function and pre-mRNA splicing—was found to be dysregulated in MPNSTs, and genetic interference experiments indicate it plays a critical role in MPNST pathogenesis. In this project, the DC will: (i) Develop tools and screening strategies to identify small molecules that modulate LSM2-8 function. (ii) Determine the biological relevance of pharmacological LSM2-8 inhibition on malignant phenotypes in MPNST models. (iii) Define the molecular impact of validated inhibitors, including their effects on LSM2-8–regulated splicing programs and disruption of LSM2-8:RNA interactions. (iv) Advance promising inhibitors toward preclinical evaluation by characterizing their molecular properties and therapeutic potential.
All the information about requirements, eligibility criteria, benefits and the selection process at https://euraxess.ec.europa.eu/jobs/461377
To apply and for more information, reach out to mscadn.decodes [at] usc.gal (mscadn[dot]decodes[at]usc[dot]gal)