Congratulations to José TOMAS AHUMADA SAAVEDRA on the acceptance of his thesis!

Summary of his research:
The most frequent and distinctive alterations found in Down syndrome (DS) are learning disability and craniofacial (CF) dysmorphism.
The CF phenotype includes reduced head dimensions, brachycephaly, reduced mediolateral orbital region, reduced bizygomatic breadth, small maxilla, small mandible, and increased individual variability. Until now, the cellular and molecular mechanisms underlying this CF phenotype remain unknown.
This thesis, using a new panel of rats and mice models proposed new candidate genes for the DS-CF phenotype.
They confirmed the role of Dyrk1a in neurocranium brachycephaly and identified the overdosage of the transcription factor Ripply3 for midface shortening through the downregulation of Tbx1, another transcription factor involved in similar phenotypes was found in Di George Syndrome.
They also defined new dosage-sensitive genes responsible for DS-CF malformations, and new models were proposed to rescue the DS-CF phenotype. This new knowledge may also lead to insights for specific brain and cardiovascular phenotypes observed in Tbx1 mutants and DS models.

Skills acquired at l'IGBMC:

• Animal experimentation (rat and mouse)
• protocol development
• Imaging techniques, microCT, 3D modeling, Voxel analysis
• Surgical techniques and dissection
• Histological techniques: inclusion, kerosene sections, histochemical and immunohistochemical techniques
• Digital microphotography
• Molecular biology techniques: PCR, real time PCR, ddPCR, Western Blot.

Life at IGBMC:
The continuous learning and cooperative environment. Something that is not easily found in other institutions.
 

Funding and partners:
This work was part of the Interdisciplinary Thematic Institute IMCBio under the ITI 2021-2028 program of the University of Strasbourg, CNRS, and Inserm.

•  Supported by IdEx Unistra (ANR-10-IDEX-0002).
• Funded through the SFRI-STRAT’US project (ANR 20-SFRI-0012).
• Backed by INBS PHENOMIN (ANR-10-INBS-07).
•  Supported by EUR IMCBio (ANR-17-EURE-0023) under the French Investments for the Future Program.

 Additional funding: Received support from the National Agency for Research and Development (ANID)/Scholarship Program/DOCTORADO BECAS CHILE/2020-72210028.
 

Future projects :
His path will continue with a postdoctoral fellowship at the prestigious Cedars-Sinai Medical Research Center, on the team of the Professor Ophir D. Klein, MD, PhD.