Grant: Operating Grant

Most of the fundamental processes occurring within living cells are mediated by large complexes of different proteins. The assembly of these complexes requires the simultaneous interaction of large numbers of protein, and (often) nucleic acid subunits. To gain a full understanding of cellular events, we must determine in atomic detail how the specific interactions between proteins are mediated and how these interactions are controlled in the assembly pathways of large complexes. Our research is directed at understanding the assembly of viruses that infect bacteria, which are known as bacteriophages. The intensive study of these types of viruses, which has been under way for more than 60 years, has led to many of the major breakthroughs in molecular biology. In this proposal we address the problem of how bacteriophages assemble their complex structures, which comprise hundreds of copies of many different proteins. Bacteriophages are very attractive for these studies because they are well characterized, we can study their assembly in a test tube, and we have recently determined the atomic structures of several of the proteins required for the assembly process. In the long term, these studies will increase our knowledge of how large protein complexes, like viruses, can assemble in a regulated fashion. Understanding this process will help us design drugs to inhibit viral growth, and will contribute to our basic understanding of how cells function.