A PhD position is available within a collaborative project between the Biomolecular Nanotechnology Laboratory, led by Prof. Aitziber L. Cortajarena at CIC biomaGUNE, and the Neurogenetics, RNA Biology and Therapies Laboratory, led by Dr. Lorea Blázquez at Biogipuzkoa Health Research Institute.
The project, “Design and evaluation of repeat RNA-binding proteins for RNA-targeting therapies (RNATher)”, aims to develop engineered RNA-binding proteins as a new platform for therapeutic modulation of disease-associated RNAs, with a particular focus on amyotrophic lateral sclerosis (ALS).
The PhD candidate will work on the design and engineering of programmable pentatricopeptide repeat (PPR) and Pumilio (PUF) proteins for sequence-specific RNA recognition and modulation. Building on preliminary proof-of-concept results, the project will investigate the ability of engineered PPR proteins to correct STMN2 RNA misprocessing, a key molecular feature of ALS, in patient-derived cellular models and in vivo.
The project will also explore AI-guided protein engineering and protein language models to generate improved PPR and PUF variants with enhanced RNA-binding properties. In addition, these programmable RNA-binding scaffolds will be engineered to incorporate new therapeutic functionalities, including targeted RNA degradation and RNA editing.
The project is highly multidisciplinary and combines research and combines protein engineering, protein biochemistry and biophysics, molecular and cell biology, RNA biology, artificial intelligence-assisted protein design, and cellular and in vivo models of neurodegenerative disease.
The successful candidate will benefit from the complementary expertise of the two participating groups: Prof. Cortajarena's group in protein design and engineering, repeat proteins, and functional biomolecular systems, and Dr. Blázquez's group in RNA biology, neurogenetics, neurodegenerative diseases and RNA-targeting therapies.
The project will be carried out jointly at CIC biomaGUNE and Biogipuzkoa Health Research Institute, two multidisciplinary and international research institutes in San Sebastian, Spain, offering state-of-the-art infrastructure and a highly collaborative research environment at the interface of chemical, biological and medical sciences.