The Institute of Biomedicine of Seville (IBiS) is a multidisciplinary biomedical research centre, with the aim to undertake high quality and competitive research at international level on the most prevalent diseases. IBIS is based on fundamental research at the molecular and cellular level with a view to promote the rapid transfer of knowledge to the clinical setting, at the same time improving the quality of clinical and epidemiological research.

The group “Neurodevelopment and Neuropaediatric Diseases” leading by Dr Patricia Ybot-Gonzalez at the Institute of Biomedicine of Seville (IBiS) in Sevilla (Spain) is interested in hosting a Marie Curie Fellowship.

Dr Patricia Ybot-Gonzalez, studied Molecular Biology and Biochemistry at the Universidad Autónoma de Madrid, PhD at the University of Liverpool, and did 2 postdocs at ICH-UCL London. In 2009 she returned as PI to Spain, where she established the Neurodevelopment group at the IBiS, and currently holds a CSIC position. Patricia has dedicated her professional career to the study of nervous system development. The results of her work are reflected in 41 publications in international journals, she has led 12 publicly funded projects as PI (3 currently in progress), 14 as collaborator, 8 HR contracts in competitive calls and has a wide network of national and international collaborations.

Description of the project to implement MSCA-PF-2025 

Our group focuses on the cellular and molecular mechanisms underlying neurulation, a key early embryonic process whose failure results in neural tube defects (NTDs), such as spina bifida and other severe congenital malformations. We study the role of the Wnt-PCP signaling pathway, particularly the Vangl2 protein, using the loop-tail mouse model carrying Vangl2 mutations. This model exhibits cytoskeletal alterations that disrupt neural tube closure. Our studies have revealed a broad spectrum of NTD phenotypes, ranging from craniorachischisis to closed defects resembling lipomyelomeningocele, the most clinically relevant form of closed NTD in humans. We have also identified pathogenic regulatory mutations in the VANGL2 gene associated with closed NTDs.  

Objective 1.- Whole genome sequencing analysis of human SB cases:  we will evaluate the region of interest (containing proximal enhancer and the promoter) in whole genome sequencing (WGS) data from 138 case (myelomeningocele) -parent trios and case-control using WGS data from 149 human cases with myelomeningocele, as well as 149 controls of similar ancestry.
Objective 2.- Validation of the mutations detected in NTD patients.  This objective builds on the results and tools obtained in previous projects of the group. After observing 4 mutations (with a prevalence of less than 1% in the population) associated with NTDs in transcriptional regulatory elements of the VANGL2 gene, our final goal is to validate these mutations using a neuroepithelial model system, derived from hiPSCs. Behaviours relevant to our study, such as apical constriction and activation of the PCP pathway during differentiation, have been successfully validated in this neuroepithelial model system.
Objective 3.- Integrative multiomic analysis of Vangl2-expressing cells during early mouse embryonic development.  In this objective, we plan to investigate in silico footprints of the homologous TFs that match locations to those identified as differentially bound by the human mutations only in Vangl2-expressing cells in mouse embryos at embryonic day (E)7-9 window.  Pijuan-Sala et al.2019, 2020 provide open scRNA-seq and ATAC-seq repositories featuring mouse embryos within the embryonic day (E)7-9 window. We will integrate independent scRNA-seq and scATAC-seq datasets from these studies, reviewing the classification and selecting cells identified as neural/neuroectodermal, where we expect to find Vangl2-expressing cells (scRNA-seq). For scATAC-seq analysis, we will examine chromatin accessibility at the Vangl2 promoter and enhancers during neurulation, specifically within the Vangl2-expressing population.
 

REQUIRED EDUCATION LEVEL and EXPERIENCE

EDUCATION 

• Degree:  Bachelor and master's degree
• Degree field:   Bachelor's degree (≥ 300 ECTS) in Biomedicine, Biology, Biotechnology, Medicine, Pharmacy and related disciplines.

RESEARCH EXPERIENCE

• Main research field: Medical science, developmental biology, bioinformatics
• Skills: cell culture, molecular biology, gene editing
• Specific requirements:  bioinformatics

• Years of research experience: 5-7 PhD research experience

   

How to apply:  Send an e-mail with the subject EoI MSCA-PF-2025 to the attention Dr Ybot (pybot-ibis@us.es) enclosing the followings documents:
o    A detailed curriculum, including a complete list of publications.
o    A cover letter describing your carrier goals and research interests, background, and qualifications.
o    Contact information (mail and phone number) of two to three referees including your PhD mentor.

   Application e-mail:  pybot-ibis@us.es