Phone: (205) 934-6593

Ph.D. 1985 (Molecular Biology), University of Wisconsin-Madison

STATUS: Currently has open positions for undergraduates.

Research Interests:

Translation Termination, Nonsense Suppression Approaches to Treat Genetic Diseases

Current Projects:

• Mechanistic studies of translation termination in yeast.

• Suppression of a nonsense mutations in mouse disease models.

• Mechanistic studies of Nonsense-Mediated mRNA Decay (NMD).

Additional Information:

Our research uses molecular biological approaches to gain a better understanding of translation termination and Nonsense-Mediated mRNA Decay (NMD)

One objective of research in Dr. Bedwell’s lab is to understand the mechanistic details of translation termination in eukaryotes. Besides the release factors eRF1 and eRF3, many other cellular components influence the process of translation termination. Surprisingly sophisticated cellular machineries also regulate the abundance of mRNAs based on the location of stop codons. We are using a combination of genetics, biochemistry, and cell biology in a yeast experimental system to better understand the molecular details of how these processes are carried out.

Second, we are investigating whether pharmacological agents can be used to suppress nonsense mutations that cause genetic diseases. First, we are exploring whether this novel therapeutic approach can benefit patients with cystic fibrosis (CF). CF is caused by mutations in the CFTR gene (which corresponds to the mouse Cftr gene). We have published several papers demonstrating that drugs can suppress nonsense mutations in the CFTR gene in various CF experimental systems, including cultured CF cell lines and a CF mouse expressing a human CFTR-G542X transgene. Most recently, we have constructed a new Cftr-G542X knock-in mouse model to explore this approach in a more physiologically relevant context.

We are also investigating whether this therapeutic approach can benefit patients with the lysosomal storage disease mucopolysaccharidosis type I-H (MPS I-H, or Hurler syndrome). MPS I-H is caused by mutations in the human IDUA gene (which corresponds to the mouse Idua gene). We have constructed a Idua-W392X knock-in mouse and have preliminary evidence that nonsense suppression can partially alleviate the primary biochemical defect that causes this devastating genetic disease.

Finally, the availability of these knock-in mouse models for CF and MPS I-H will allow us to explore whether the suppression of Nonsense-Mediated mRNA Decay (NMD) can further enhance the therapeutic effect provided by nonsense suppression agents. It is hoped that either nonsense suppression alone or in combination with NMD suppression will ultimately provide a therapeutic benefit for a broad range of human genetic diseases caused by nonsense mutations.

To find out more about Dr. Bedwells's research please visit here