PCI2021-122042-2B
Financiado
UNDERSTANDING THE EFFECTS OF MUTATIONS ON DYNAMIC INTERACTIONS UNDERLYING TRANSC...
UNDERSTANDING THE EFFECTS OF MUTATIONS ON DYNAMIC INTERACTIONS UNDERLYING TRANSCRIPTIONAL REGULATION
MANY FUNCTIONS IN BIOLOGY ARE CARRIED OUT WHEN DIFFERENT MOLECULES, SUCH AS PROTEINS, INTERACT WITH EACH OTHER. ONE AREA WHERE INTERACTIONS BETWEEN DIFFERENT PROTEINS IS VERY IMPORTANT IS THE REGULATION OF GENE EXPRESSION. THIS IS...
MANY FUNCTIONS IN BIOLOGY ARE CARRIED OUT WHEN DIFFERENT MOLECULES, SUCH AS PROTEINS, INTERACT WITH EACH OTHER. ONE AREA WHERE INTERACTIONS BETWEEN DIFFERENT PROTEINS IS VERY IMPORTANT IS THE REGULATION OF GENE EXPRESSION. THIS IS A HIGHLY COOPERATIVE PROCESS BETWEEN DIFFERENT BIOLOGICAL MOLECULES, AND OFTEN INVOLVES INTERACTIONS THAT ARE FLEXIBLE, DYNAMIC, AND POORLY UNDERSTOOD. TO DATE, MUCH OF OUR KNOWLEDGE ABOUT PROTEIN INTERACTIONS HAS BEEN DEFINED BY A "LOCK-AND-KEY" MODEL, WHERE A PROTEIN'S STRUCTURE DETERMINES HOW IT INTERACTS AND FITS INTO ITS PARTNER PROTEIN TO CARRY OUT A FUNCTION. WHILE THIS MODEL HAS ALLOWED US TO UNDERSTAND MANY IMPORTANT PROTEIN INTERACTIONS, IT DOES NOT ADEQUATELY EXPLAIN HOW DYNAMIC PROTEIN INTERACTIONS OCCUR. HERE, I PROPOSE TO GAIN A BETTER UNDERSTANDING OF DYNAMIC INTERACTIONS BETWEEN PROTEINS THAT ARE INVOLVED IN GENE EXPRESSION. I WILL DO THIS USING STATE-OF-THE-ART METHODS IN WHICH WE CAN SYSTEMATICALLY MAKE MANY THOUSANDS OF MUTATIONS IN PROTEINS THAT ARE INVOLVED IN SUCH INTERACTIONS, AND DIRECTLY ASSAY HOW THE MUTATIONS AFFECT THESEINTERACTIONS AND DOWNSTREAM BIOLOGICAL FUNCTION. USING THIS DATA, WE CAN BEGIN TO UNDERSTAND THE STRUCTURE AND MECHANISM OF SUCH INTERACTIONS. WE WILL GAIN ACCURATE MODELS FOR HOW AFFINITY AND SPECIFICITY OF DYNAMIC INTERACTIONS ARE ENCODED IN SEQUENCES, WITH IMPORTANT IMPLICATIONS FOR DISEASES WHERE SUCH INTERACTIONS ARE MIS-REGULATED (E.G. CANCER). EEP MUTATIONAL SCANNING\FUNCTIONAL GENOMICS\INTRINSICALLY DISORDERED
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Línea de financiación: concedida
El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2021-01-01
Presupuesto
El presupuesto total del proyecto asciende a
161K€
Líder del proyecto
FUNDACIO PRIVADA CENTRE DE REGULACIO GENOMICA
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