鈥淔IFTY years from now, we鈥檙e going to have kind of Disneyland models of
cells鈥攐n computers or in some bigger form,鈥� predicts immunologist Philippa
Marrack of the University of Colorado, Denver. 鈥淓ventually, what we鈥檙e going to
build is a cell that鈥檚 so big you can see it. I don鈥檛 want this just to be on a
computer, I want this to be a building. I want this to be a walk-through.鈥�
This vision extends beyond Marrack鈥檚 own area of expertise鈥攖he body鈥檚
immune defences鈥攖o anyone studying how cells stay alive. 鈥淚t鈥檚 kind of
like the Human Genome Project of the cell world,鈥� she says. The goal will be to
reveal where and how each protein among thousands is acting inside the cell at
any moment.
But which of the millions of different types of cell should scientists
recreate first? A prime candidate, in Marrack鈥檚 view, is the lymphocyte, or
white blood cell, which fights infectious agents such as viruses and bacteria.
Somehow, without ever having encountered the invaders before, specialised
lymphocytes called T cells recognise them as foreign and mount a rapid
response.
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In 1987, Marrack and John Kappler showed that only a fraction of all the T
cells that begin to develop before birth live long enough to become mature
fighters. The majority are designated unsuitable for action and die off. The
reason is that they have the dangerous potential for reacting against the body鈥檚
own tissues, which could trigger diseases such as rheumatoid arthritis.
This work laid the foundations for immunologists to ask what happens to those
T cells that are allowed to mature. How does the body keep T cells alive, with
their memory of past infections, to protect us into old age? And also, what then
stops the response to an infection from getting out of control? The answers
involve proteins called cytokines, which Marrack has helped to identify. 鈥淲e
know that the memory T cells are responding to cytokines and it鈥檚 the balance of
cytokines that鈥檚 slowly moving them along,鈥� she says.
Marrack predicts that scientists might some day use cytokines to boost the
number of memory T cells that react to a particular vaccine. This could work not
only for warding off infection but also to fight cancer, as some types of cancer
display surface proteins that T cells recognise as foreign.
Meanwhile, Marrack is contributing to the giant walk-through cell model by
spying on proteins in motion inside living T cells. Using a technique called
live fluorescence imaging, Marrack has found, for example, that when T cells
recognise their targets, a protein called MEKK2 helps transmit signals around
the cell to trigger the production of new proteins.
This is just one small step in the long sequence of events that enables T
cells to fight infection. But it is only by identifying all the proteins
involved that immunologists will work out how we fight disease. The giant model
of the future will be a total view of what鈥檚 going on inside the cell. 鈥淚t has
to be,鈥� Marrack insists. 鈥淥therwise why are we doing all these experiments?鈥�
