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“This work provides the means to understand how the malaria parasite is able to survive in the red blood cell and obtain nourishment and hide from the host defense systems.”
~Alan F. Cowman |
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So it really started from the need to know the sequence
information for trafficking so that we could make genetic mutants in
a way that the specific altered protein was still trafficked to its
normal location.
Your
2004 Science paper was chosen as a "New Hot Paper" by
Essential Science Indicators, and your 2003 Science
paper ranks #2 on our listing of the most-cited malaria papers
published in the past two years. Would you talk a little bit about how
these papers are related (if at all), i.e., does the 2004 paper
build on the discoveries in the 2003 paper, etc.?
The 2003 Science paper is from Geoff's McFadden group, and
I played only a collaborative role in assisting them with their
setup for genetically manipulating P. falciparum. The
McFadden group is particularly interested in the function of the
apicoplast and has used trafficking motifs to identify the proteins
directed to this organelle.
They are actually not related at all in terms of their biology.
The link is in the technology used to dissect the trafficking motifs
and then using this bioinformatically to identify the relevant
proteins.
Why
do you think your 2004 Science paper is highly cited?
Because it answers a fundamental piece of biology with respect to
an important pathogen. It also allowed the identification of a large
number of proteins exported into the host cell. This has provided
the means to analyze and determine the function of these proteins
which are important for the parasite’s survival and the pathogenic
effect it has on the host.
Does
it describe a new discovery or a new methodology that's useful to
others?
Yes, it has identified most if not all proteins exported into the
host erythrocyte and this has activated a large amount of work to
determine their function.
Could
you summarize the significance of your paper in layman's terms?
This work provides the means to understand how the malaria
parasite is able to survive in the red blood cell and obtain
nourishment and hide from the host defense systems. It therefore has
the potential to develop new treatments to interfere with these
processes and the survival of the parasite.
How
did this particular paper come into being, and were any problems
encountered along the way?
We have been working on malaria for a long time and one of our
aims is to understand how the parasite can survive in the human
host. In order to accomplish this we wanted to make mutant parasites
that lacked or expressed altered forms of particular proteins. To do
this properly we needed to know how proteins were trafficked out
into the red blood cell, and this led directly to this avenue of
investigation.
What
sorts of antimalarial treatments do you expect might be developed as a
result of your protein targeting research?
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A
scanned electro microscopy shot of a red blood
cell infected with malaria. |
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We are really discovering new biological features of the malaria
parasite, and these are related to how they cause disease. Whilst
any new treatments from this work are not even on the horizon we
commenced it with the hope that we could identify potential new drug
targets. The fact that we have been able to identify virtually all
proteins exported by the different Plasmodia species to their
respective host cell means that we could essentially compare their
"exportomes." Comparison of them would help identify those
that are conserved across the different species and are therefore
functionally important and some of which may be potential drug
targets.
Would
they be preventative vaccines or more geared towards post-exposure
cures, and will drug resistance be an issue?
It really is too early to talk about any possibilities with
respect to this, but drug resistance will always be an issue in the
development of any new drugs against a microbe.
If
applicable, what are the social or political implications of your
research?
Having identified all or most of the proteins exported by the
malaria parasite we can now start to investigate their function, and
this has important implications for the development of treatments to
interfere with this process.
How
has this research changed since you first started working in the
field?
The biggest change has come from the availability of the genome
sequence of a number of malaria parasites and it is resulting in a
leap in our understanding of how the parasite infects humans and
causes disease. The genome sequences has provided a huge amount of
information and given us the ability to use the information we have
gained in building the global picture of exported proteins in
Plasmodia.
The second important change has come from the ability to
genetically manipulate the parasite, a tool we have not had all that
long compared with other areas of biology. It really has provided us
with an important technological leap forward and opened many
possibilities to dissect the parasite.
Where
do you see this work going in 5 or 10 years?
I think it is an amazing time to be in malaria research, and
science in general, because of the genome information and the
increasing number of technological advances. The availability of the
genome information from the human host as well as the mosquito
vector and the malaria pathogens really is driving a revolution in
understanding the parasite’s interaction with both the host and
vector. Our ability to genetically manipulate the parasite will
increase, and this will increase our ability to directly ask major
questions relevant to infection and pathogenesis.
Professor Alan Cowman
Head, Division of Infection and Immunity
The Walter and Eliza Hall Institute of Medical Research
Melbourne, Australia
n
the interview below, Professor Alan Cowman talks about his
highly cited work in malaria research. Two of his papers in
particular have been singled out by Special Topics:
"Dissecting apicoplast targeting in the malaria parasite Plasmodium
falciparum," (Foth BJ, et al., Science
299[5607]: 705-8, 2003), which ranks #2 on the 2-year papers
list in the Malaria Special Topic, and "Targeting malaria
virulence and remodeling proteins to the host
erythrocyte," (Marti M, et al., Science
306[5703]: 1930-33, 10 December 2004), which was selected this
month as the 
,
Professor Cowman’s record includes 57 papers cited a total
of 1,873 times to date in Microbiology. He is the Head of the
Division of Infection and Immunity at the Walter and Eliza
Hall Institute of Medical Research in Melbourne, Australia.
