Throwing the Wrench With Perfect Aim
As a child growing up in the small town of Pincourt, Quebec, Annick Gauthier knew two forces would guide her life: she was fascinated by how the body works, particularly diseases, and she wanted to help people. At first she thought she'd be a pathologist. No, she realized later, that's too late in the disease process. She wanted to prevent disease. To understand the first deadly kiss between pathogen and human cell in such intimate detail that she could throw a wrench into the molecular works.
 "I'm interested in understanding what's happening at the most basic biochemical level. If we can figure out how for example the Hepatitis C virus actually uses the body to reproduce itself, then we can set up roadblocks that stop the culprit from acting," says Dr. Gauthier, winner of the 2005 NSERC Howard Alper Postdoctoral Prize.
In the late 1990s, Dr. Gauthier's passion for disease biochemistry led her to Ph.D. research in the lab of University of British Columbia microbiologist Dr. Brett Finlay, a world leader in the study of the interaction between bacteria and their human "host" cells. She arrived at an exciting time. Dr. Finlay's lab group had just made a major discovery about enteropathogenic E. coli, a major cause of infantile diarrhea that kills an estimated 100,000 children a year worldwide.
Surprisingly, unlike most bacteria, enteropathogenic E. coli uses its own protein to attach to a host cell. It's like installing a door and having the key. Dr. Gauthier set her sights on determining how the bacterium inserts this protein. Through six years of research she determined that a group of bacterial proteins called the type III system act as a superhighway to deliver the bacterial attachment protein into the human cell in a single step. The finding is exciting in that the type III system only exists in pathogenic bacteria, and thus might be an ideal target for vaccines or antibiotics.
For her present postdoctoral work, Dr. Gauthier decided to switch her focus to tackle an even more difficult scourge: the hepatitis C virus.
"I want to use what I learned from bacteria and apply it to virology. I think that this brings a fresh perspective to the problem," she says from New York where's she's working in the virology lab of Dr. Charles Rice, an internationally-acclaimed researcher, at The Rockefeller University. "Often people think about viruses as inert substances, but I think there's a real interplay going on between the virus and the host."
Approximately 3 per cent of the world population, a staggering 170 million people, including many Canadians, are infected with the Hepatitis C virus. It's a chronic infection which often leads to cirrhosis or liver cancer. There's presently no vaccine or even effective therapy for the disease.
Dr. Gauthier's postdoctoral research, now in its second year, is focused on understanding how a remarkably simple virus – a strand of RNA that encodes only ten proteins – hijacks our liver's cellular machinery while staying hidden from our immune defences. Using her experience with E. coli, she has focused on a particular protein, dubbed NS4B.
She suspects it might be the trigger for the creation of a web-like structure that develops in infected liver cells. And since she has already determined that the virus can't replicate when NS4B is experimentally deleted, the protein could also be the ideal target for future therapies.
Says Dr. Gauthier: "My hypothesis is that NS4B interacts with host cell proteins to create this membranous web and that's the site for viral replication. So I want to figure out how it's doing it."
Contact:
Dr. Annick Gauthier
E-mail: gauthia@mail.rockefeller.edu
|
