The research carried out in laboratory of Dr. Philip Smith at UT Southwestern focuses on the folding, structure, and function of integral membrane proteins and their misfolding as the basis of human disease. The cystic fibrosis conductance regulator (CFTR) and archaebacterial homologues serve as models for biophysical, molecular biological, and cell biological studies directed at understanding these processes. These proteins are members of the ABC transporter supergene family of ATP-dependent active transporters and channels. This supergene family is the largest in many of the completely sequenced microbial genomes and includes many medically relevant members, including ATP-driven drug and lipid pumps and bacterial toxin transporters, in addition to the CFTR channel. Mutations in cftr (>1,000 to date) cause the fatal recessive disorder cystic fibrosis (CF). Many of these mutations alter the ability of this membrane protein to efficiently fold into a functional structure. Others alter coupling of ATP to the transmembrane solute pore. Understanding these defects at a molecular level is providing insight into how primary sequence encodes the folding pattern of integral membrane proteins and how the energy of ATP hydrolysis is utilized to effect movement of a solute across a membrane barrier. In addition, the system is providing insight into the mechanisms that cells employ to recognize and process misfolded proteins.
Source: http://profiles.utsouthwestern.edu/profile/17274/philip-thomas.html
