Bacteriophages are parasites of bacteria, and the world’s most numerous organisms. There are estimated to be 1031 phages worldwide. Compare that to 1021 stars in the universe. Phages affect us in many different ways. For example, approximately half of all bacteria are killed daily by phages. Phages can carry virulence and antibiotic resistance genes for pathogenic diseases, such as cholera, diphtheria and scarlet fever. Phages can also be used therapeutically against pathogenic diseases. Many of the major discoveries of the molecular biology revolution were made possible using phages.
Our mission is to understand bacteriophage development, life history, population dynamics and evolution. We also use phages as biological models for pathogenic viruses. Of particular interest is exploring the process of virus emergence and developing antiviral and antibacterial therapeutics.
Population Dynamics and Evolution of Infectious Diseases
Fifty to one hundred million people, or ~5% of the world’s population died when the last major influenza pandemic swept the globe in 1918. Since then the world’s population has increased by 4.5 billion and its connectivity prompts the term “global village”. If, in today’s world, direct contact transmitted HIV can cause ~60 million infections and ~30 million deaths, then a highly virulent airborne virus would be catastrophic. Unfortunately it is not a case of if, but when. Yet our understanding of emerging infectious diseases has only increased superficially since 1918. We still have no answers to basic questions. Why and how do viruses switch hosts? Why do some viruses, such as HIV, spread pandemically through populations whereas others, such as influenza A virus H5N1, appear briefly before petering out? How do viruses evolve in mixed host populations? These questions can be addressed using theory from evolutionary ecology. To explore emergence from an evolutionary ecological perspective, we study the dynamics of bacteriophage phi6 infection of a native host Pseudomonas phaseolicola and a novel host P. pseudoalcaligenes. The long term goal is to understand the population dynamics of viral adaptation to new host types.
Mycobacterium tuberculosis is a major public health threat. In 2010, an estimated 8.8 million persons contracted TB, and 1.5 million succumbed to the disease. In line with the adage “the enemy of your enemy is your friend”, we are isolating and fully sequencing mycobacteriophages in order to determine the molecular basis of host range, and to identify any novel genes that may permit manipulation or neutralization of M. tuberculosis.
Life History Stochasticity
Bacteriophage λ lyses its host Escherichia coli through the activity of a protein called holin, which forms holes in the bacterial membrane at a genetically encoded time. Our analysis confirms that stochastic holin expression can account for variation in lysis timing. Furthermore, we find that the holin lysis system contains several features designed to minimize noise. We are exploring how modification of holin transcription and translation affects the mean and variation of lysis timing.