A 4-year-long contract is available for a thesis project supervised by Dr. Francisco J Blanco studying the structure-function of two proteins relevant for human health and disease.
THE PROJECT
The alfa subunits of heterotrimeric G proteins act as molecular switches by their ability to bind and hydrolyze GTP, and their dysregulation causes cancer. We will study the molecular recognition of inhibitors of two such proteins: Gai3, which promotes breast cancer metastasis when overactivated by regulatory proteins, and Ga11, which causes uveal melanoma when overactivated by mutations. The ultimate aim is to facilitate the development of therapeutic molecules. Protein samples will be prepared for structural characterization by NMR, crystallography, and other techniques. Functional assays in cancer cells are planned with our collaborator at Boston University during a 4-month-long stay.
STARTING DATE (tentative): January 2025
REQUIREMENT: Master of Science
The alfa subunits of heterotrimeric G proteins act as molecular switches by their ability to bind and hydrolyze GTP, and their dysregulation causes cancer. We will study the molecular recognition of inhibitors of two such proteins: Gai3, which promotes breast cancer metastasis when overactivated by regulatory proteins, and Ga11, which causes uveal melanoma when overactivated by mutations. The ultimate aim is to facilitate the development of therapeutic molecules. Protein samples will be prepared for structural characterization by NMR, crystallography, and other techniques. Functional assays in cancer cells are planned with our collaborator at Boston University during a 4-month-long stay.
STARTING DATE (tentative): January 2025
REQUIREMENT: Master of Science
CONTACT: fjblanco@ibv.csic.es
THE HOST GROUP AND INSTITUTION
The Biomolecular NMR group is part of the Department of Molecular Basis of Disease at the Instituto de Biomedicina de Valencia, IBV-CSIC
The laboratory is at the Centro de Investigación Príncipe Felipe (associated unit to IBV), located in the Ciutat de les Arts i les Ciènces in Valencia, a city with a rich history and a high standard of living.
Publications of the group relevant to the project:
o Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif. Ibáñez de Opakua et al (2017) Nature Commun 8, 15163. Doi: 10.1038/ncomms15163.
o The Gαi-GIV binding interface is a druggable protein-protein interaction. DiGiacomo et al. (2017) Sci Rep 7, 8575. Doi: 10.1038/s41598-017-08829-7.
o Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer. Zhao et al. (2023) PNAS 120, e2213140120. Doi: 10.1073/pnas.2213140120.
Full record of the group:
Further information in Spanish:
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Francisco J Blanco
Biomolecular NMR
Instituto de Biomedicina de Valencia (IBV) CSIC
Jaume Roig 11, 46010 Valencia, Spain
Unidad Asociada Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera 3, 46012 Valencia, Spain
Phone: 34 963289680, ext. 2112
fjblanco@ibv.csic.es
https://www.ibv.csic.es/en/project/biomolecular-nmr/
Francisco J Blanco
Biomolecular NMR
Instituto de Biomedicina de Valencia (IBV) CSIC
Jaume Roig 11, 46010 Valencia, Spain
Unidad Asociada Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera 3, 46012 Valencia, Spain
Phone: 34 963289680, ext. 2112
fjblanco@ibv.csic.es
https://www.ibv.csic.es/en/project/biomolecular-nmr/