Eddie Holmes joins the School of Biological Sciences

5 October 2012

Professor Edward Holmes arrived in Sydney in October to begin work with the School of Biological Sciences and the Sydney Institute for Emerging and Infectious Diseases on the Australian Disease Database.

Eddie, as he prefers to be known, studies viruses. He works to understand their evolution, epidemiology and emergence.Eddie works on any number of viruses that infect any number of hosts. "In the early part of my career I was most interested in human immunodeficiency virus (HIV) and hepatitis C virus. In recent years I have published mostly on influenza, dengue and rabies. Currently, I am doing a lot of work onmyxoma virus, the cause of myxomatosis in Australian rabbits."

Professor Eddie Holmes
Professor Eddie Holmes

But Eddie's interest is not simply a collecting and cataloguing exercise - although that is part of it; he refers to himself as doing 'applied' evolutionary biology. "RNA viruses evolve rapidly - around a million times faster than human DNA. This allows us to effectively watch evolutionary change in 'real-time'," exclaimed Eddie. "It's like pushing the 'fast-forward' button on a DVD player. They are fantastic playgrounds for evolutionists."

The majority of Eddie's research is on RNA viruses - the most common cause of emerging disease. "The main differences between RNA viruses and other organisms are that RNA viruses evolve incredibly rapidly and are extremely small." In addition, the enzyme responsible for RNA replication, RNA polymerase, is very error prone. This leads to more mutations and therefore faster evolution. "Viruses evolve in the same way as other organisms, through a combination of mutation, natural selection, recombination and migration. So, the 'classic' rules of evolution can be applied as much to viruses as they can to plants and animals."

"I study virus evolution in a number of ways but always using comparative approaches. That is, I compare the gene and genome sequences of different viruses. My main tool is the phylogenetic tree, which contains an enormous amount of evolutionary information." A phylogenetic tree is rather like a family tree; if two species have very different genome sequences, they will be placed on very distant branches, which shows a very distant relationship. "The beauty of phylogenetic trees is that they can tell you so much more. With a few analytical tricks you can use them to deduce where a virus has come from, the direction it has spread through a population, how quickly it has evolved, and even how rapidly its population size has grown."

Of particular interest to Eddie, is how viruses are able to jump species boundaries and emerge in new hosts. "Whether or not a virus is able to jump species boundaries reflects a complex interplay between ecology and genetics" he said. There needs to be opportunity in terms of both genetics and contact (for an example of an unusual contact having fatal consequences, read the news story here). But Eddie is mostly interested in establishing the genetic ground rules for how a virus can or cannot establish a productive infection.

"A simple example of such a rule is that the closer two host species are, then the more likely that a virus will be able to jump between them," explains Eddie. This is because the cells and cell receptors, which a virus infects, diverge along with their hosts. "Hence, most human viruses come from other mammals, whereas none come from plants." Eddie recommends reading David Quammen's new book Spillover, for those interested in a readable account of emerging viruses. "I am also interested in how the virulence of viruses changes when they jump species boundaries."

Arriving at Sydney University from Pennsylvania State University, Eddie is joining the School with a $4 million National Health and Medical Research Council Australia Fellowship. "I want to apply my knowledge of emerging viruses to the practical situation in Australia," he said. "A number of important infectious diseases have emerged recently in the Asia-Pacific region, so emerging viruses are likely to be an important issue for Australia."

"To help determine how a new virus may spread through Australia I plan to create a unique new database that will integrate information on the landscape, demographic, behavioural and socioeconomic features in Australia that are likely to have a major impact on disease transmission." This Australian Disease Database will include information on population densities, directions and magnitude of flight traffic, major road networks and landscape features such as the Great Dividing Range. "I hope that this database will make it possible to predict how quickly and in what directions any new or existing pathogen will spread once it reaches Australia."