Basic cell biology
For AHFMR Scientist Dr. Richard Wozniak, it's all about the nucleus. "The nucleus is the 'brains' of the cell. It contains the genetic material, and controls the cell by regulating gene expression. In my lab we study nuclear transport-the mechanisms by which things get in and out of the nucleus."
While much of Dr. Wozniak's work at the University of Alberta has clear implications for cancer research, a significant part is relevant to the quest for a better understanding of HIV infection. When a virus enters a cell, one of its main targets is the nuclear transport machinery: the proteins that control what gets across the membrane of the nucleus. In some cases, viruses just take over the machinery for their own benefit, so that they can get whatever they need into the nucleus. In other cases, such as with HIV, the virus not only usurps the machinery, it interferes with nuclear transport. In turn, this can interfere with the immune response and, therefore, the body's ability to fight off the virus.
But before scientists can understand what goes wrong with nuclear transport in HIV infection, they must know exactly how nuclear transport works. It differs from transport across other types of cell membranes; that's because things don't actually cross a membrane in nuclear transport. The nucleus is surrounded by two membranes that form an envelope. At certain points around the nucleus, the envelope is fused and forms a hole-a bit like the hole in a doughnut. This complex structure, made up of proteins, is called the nuclear pore complex (NPC). The nucleus is dotted with about 5,000 NPCs. They are the gateways in and out of the nucleus.
Viruses target certain proteins in the NPCs, altering the nuclear transport machinery and allowing the virus into the nucleus. One of the things a cell does in response to a virus is to change the composition of the nuclear transport machinery, so as to retain some resistance to the virus.
"This is very complicated," notes Dr. Wozniak. "Because the virus is using the machinery, and because the machinery is part of the response to the virus, we need to know more.
"We're at the initial stages now-the work with viruses represents a new direction for my lab. Most of our effort to date has focused on identifying the molecular players in nuclear transport. As that situation has become clearer, we're starting to look at what the players are doing in response to a virus. In this regard, we are excited about some recent results. We have identified proteins that may play a role in the cellular defence against viruses. In the long term, we may be able to disrupt the virus's ability to control the cell by manipulating nuclear transport."