David Baillat

Publications

Affiliation: Department of Biochemistry & Molecular Biology
Tel: (409) 772-6330
dabailla@UTMB.EDU
Route:
5.106 BSB

David Baillat, Ph.D.

Assistant Professor

Area of Research

The focus of our research is the elucidation of the role of the Integrator Complex in the biogenesis of the U-rich small nuclear RNAs (UsnRNAs) and in the regulation of RNA polymerase II (RNAPII)-mediated transcription. Our ongoing work includes biochemical, molecular biology and genome-wide approaches to characterize its structure and function. More recently we have also been led to investigate the role of the Integrator Complex during development through the characterization of mutations in several Integrator Subunits that are associated with severe developmental defects.

Research focus 1. Molecular Mechanisms of Integrator Complex Function.

Integrator is a metazoan-specific complex containing at least 14 subunits and interacting with the CTD or the RNA polymerase II. A majority of its subunits remains largely uncharacterized structurally and functionally. A primary goal of my research is to understand how its main functions in snRNA processing and RNAPII transcription are carried out. Using the Human and Fly Integrator complex as models we intend to i) determine its structure and the network of intermolecular interactions underlying this structure using cryo-EM and protein crosslinking coupled to mass spectrometry (XL-MS); ii) identify the subunit(s) involved in the RNAPII CTD recognition; iii) understand how Integrator specifically recognizes UsnRNA promoters using immobilized template assays and mass spectrometry; iv) use genome-wide approaches (RNA-deq, CLIP-seq and ChIP-seq)  to understand how Integrator regulates RNAPII transcription.

Research Focus 2. Role of the Integrator Complex in Development.

In collaboration with clinicians in the United States, Europe and Israel we have identified mutations in distinct Integrator subunits that are associated with severe developmental defects. It is the first time that Integrator mutations are found associated with a human disease. Thus, they represent an unprecedented opportunity to study the inner mechanics of the Integrator complex and its impact on the physiology of the cell and on development. Using a combination of biochemistry, molecular biology, genome editing and genome-wide approaches, we intend to develop animal and molecular models to dissect the role of the Integrator Complex in human development and in the pathologies associated with these mutations