Francis Nano, PhD

Professor, Biochemistry/Microbiology Department
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Phone: (250) 721-7074
Lab Page
Research area: Type VI secretion in gram negative bacteria, temperature-sensitive vaccines using Arctic genes.

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Research Profile

New secretion system discovered

Right from the inception of microbiology, researchers have recognized the importance of bacteria toxins. For example, botulism toxin has been studied since the 1800s. What amazes Dr. Francis Nano, is that while microbiologists had isolated numerous toxins as far back as the 1940s, it never occurred to them earlier to focus on how bacteria secrete toxins. Given the early focus on toxins, it is a little weird that basic secretions systems are still being discovered in pathogenic bacteria, but incredibly, they are.

Secretion systems are common to all cells. They consist of a complex of proteins that sit in the cell wall and form a channel, allowing the cell to preferentially secrete certain proteins that have some beneficial action in the surrounding area.

Nano’s lab recently helped discover a new secretion system in gram negative pathogenic bacteria, which many researchers think is involved in secreting toxins. This is exciting because if you could disrupt a toxin secretion system, you could have a drug that worked against very different types of bacteria secreting a plethora of toxins.

Nano works with two species of bacteria, a safe strain of Francisella tularensis (wild strains cause tularemia) and Mycobacterium tuberculosis, which causes tuberculosis. Both F. tularensis and M. tuberculosis evade immune systems by living inside macrophages, the cells of the immune system that engulf and digest invading bacteria. Nano wanted to know what a microbe would need to live in a human cell, so he began looking for genes that are involved, and in 2004, he found a group of genes that F. tularensis depends on to survive in macrophages. The genes were clustered together in a way that geneticists call a pathogenicity island. Pathogenicity islands are often conserved in evolution and passed on to other species of bacteria.

By searching sequence databases, he and other researchers soon discovered related pathogenicity islands in 60 different types of bacteria, presumably serving the same function. Then in 2006, researchers at Harvard showed that genes in the related pathogenicity island in Vibrio cholera (which causes cholera) codes for a secretion system, now called the Type VI secretion.

Although there is a good chance this system secretes toxins, it probably does more than that. Nano’s lab is currently working on identifying what proteins are secreted by Type VI secretion and why they are so important for helping F. tularensis survive in macrophages.

Artic bug offers vaccine strategy

In the late nineties, Dr. Francis Nano asked a Canadian polar expedition headed by Ron Verrall to pick up some Arctic Ocean water. Nano wanted to find out what type of bacteria could survive such extreme cold.

The team, who were interested in sonar recordings of the ocean below the ice, had several Artic camps along a 180 km stretch of ice off the coast of Allert, Ellesmere Island, the most northern outpost of Canada. During one of their daunting journeys where they lived in heated tents, they cut through the thick ice near the North Pole and collected several thermoses full of ocean water (which quickly froze) and couriered them back to UVic. The water was still frozen when it arrived in Nano’s lab.

Not surprisingly, the water was practically free of life, but Nano managed to isolate some samples of bacteria, five of which he has identified. One of them was Shewanella frigidimarina, a cold-water bacterium found in icy waters around the world.

One of the strange things about cold-water bacteria like S. frigidimarina is that they can only grow in cold water. Many of Nano’s isolates die at temperatures above 18oC. Nano has identified several proteins from Arctic bacteria that make them sensitive to warm temperatures. When Nano realized he could use these proteins to create a safe live vaccine, his Arctic bacteria work collided with his other interests: tuberculosis and tularemia.

The idea of a live, temperature-sensitive vaccine is not new: the strategy is to create a strain of pathogen that can that replicate in a person’s skin, but not penetrate into deeper tissue to cause an infection. This way a person’s immune system is safely exposed to the pathogen, giving them future immunity. A live vaccine gives better protection than a dead one since the immune system gets exposed to the intact organism.

Nano has moved one of the genes that confer temperature sensitivity into F. tularensis, making it unable to grow at higher temperatures. Nano and a collaborator are currently testing this live vaccine for its ability to stimulate the immune system.

Nano’s main goal is tuberculosis; he will try the same strategy in M. tuberculosis. The current vaccines for tuberculosis are poor, especially in protecting against tuberculosis in adults.