The team will develop methods to accelerate the pace of discovery of genetic determinants for cardiovascular disease.
The modifications conferred during HS biosynthesis were thought to be the sole determinants of HS structure until the discovery of the cell surface HS editing enzymes known as the Sulfs [7].
The approach can achieve very fine scale resolution, unmasking genomic features and leading to the discovery of determinants of recombination rate variation.
Mutagenesis studies performed on FSLLSH with natural and non-natural amino acid substitutions led to the identification of critical EPO-binding determinants, and the discovery of new peptide ligands.
Analysis of the subtype-specific ligand receptor interactions allowed identification of the major determinants of ligand selectivity, which may facilitate discovery of more efficient drug candidates.
Theoretically, this will result in a higher yield in the discovery of genetic determinants of complex traits.
Our results demonstrate that methods based on accumulations of rare variants discovered through re-sequencing offer substantially greater power than conventional analysis of GWA data, and thus provide an exciting opportunity for future discovery of genetic determinants of complex traits.
This line of research has, for example, led to the discovery of genetic determinants of IFN-responsiveness 79– 82 and to the identification and characterization of key molecules in antiviral defense, such as the signaling molecule MAVS 83 and a broad spectrum of antiviral IFN-stimulated genes.
We test novel strategies for nerve remyelination and regeneration, study chemical and structural correlates of neuronal hyperexcitability, examine the molecular determinants of axonal integrity, and translate our discoveries to the clinic.
The paths to discovery of the genetic determinants of common disease are now on firm ground.
This proof of concept in a perennial organism opens up opportunities for discovery of novel genetic determinants of economically important but complex traits in plants.
