Perforins, Biomedical Computing, and Cancer Research

(Figure Caption: Cell apoptosis involving perforins. Source: student.ccbcmd.edu/.../images/adccapoptype2.gif)


I am engaged in biomedical research, particularly in biomedical computing and imaging. My doctoral thesis (in the area of mathematical and computational biophysics) at Monash University (Melbourne, Australia) deals with cell motility, which has implications to the immune system and cancer research.

At the Mathematics Department of Ateneo de Manila University I advise students (undergraduate, masteral, and doctoral levels) doing research in applied mathematics, computational science, and computer science. Some of my students and I have done studies on modeling tumor growth using cellular automata. At present, I have a doctoral student (doing Ph.D. in Mathematics) investigating mutations and other aspects of cancer growth.

I am also collaborating with medical doctors at Medical City, an affiliated hospital of Ateneo de
Manila University. Our research involves medical imaging including magnetic resonance imaging (MRI) and digital mammograms. I have another doctoral student (doing Ph.D. in Computer Science) who is investigating certain aspects of mammography and grid computing.

Also, I am a co-principal investigator in the ONCO-MEDIA project ( See: http://www.onco-media.com/ ), an international project which is in the area of content-based medical image retrieval with biomedical applications using grid computing.

Recently, I encountered a feature article (Monash University eNews) on perforins done by Monash University researchers. These researchers have found that human immune proteins crucial for fighting cancer, viruses and bacterial infections belong to an ancient and lethal toxin family.

Below is an excerpt from the feature article:

(Source:http://www.monash.edu.au/news/newsline/story/1210)

[startofquote]

Toxic shock: immune system's anthrax link

Human immune proteins crucial for fighting cancer,
viruses and bacterial infections belong to an ancient
and lethal toxin family previously only found in
bacteria, Australian researchers have found.
These proteins, called perforins, are related to
bacterial toxins that cause diseases such as anthrax,
gas gangrene and scarlet fever. The discovery was made
by a team led by Professor James Whisstock and Dr
Michelle Dunstone from Monash University's School of
Biomedical Sciences.

Professor Whisstock, winner of the 2006 Science
Minister's Prize for Life Scientist of the Year, said
the team was stunned when it became clear that the
bacterial toxins and perforins had a common ancestor.

"Over millions of years of evolution bacteria
developed these proteins as weapons of attack," he
said.

"But animals have evolved these proteins for defence
against that attack. It's a molecular arms race and
there's still no clear winner."

Professor Whisstock said perforins were so-called
because they kill bacteria, virally-infected cells and
cancerous cells by punching tiny holes that perforate
them.

"People who lack one of these perforins can develop a
serious blood disease called hemophagocytic
lymphohistiocytosis and may be predisposed to develop
cancer," he said.

"Perforins are also dangerous molecules. They can
create absolute havoc in the immune system if they're
not controlled properly. By understanding how they
work we can find ways to control them in infectious
diseases and areas such as transplantation rejection."
Using X-ray crystallography, the team worked out the
structure of a perforin called Plu-MACPF, which, due
to its similarity to the bacterial toxins, told them
how the whole perforin family worked. Their findings
are published today in the international journal
Science.

Dr Dunstone said the findings were the culmination of
nine years of research.

"Now we finally know what perforins look like and how
they work, we can use this knowledge to develop new
ways to fight disease," she said.

Professor Whisstock said certain perforins were not
only important for defending humans against attack by
bacteria and viruses, but also important for
propagating the human species because of their role in
embryo implantation.

"It is ironic that we fear diseases such as anthrax,
yet from the same family of toxins comes a protein
that is central to human reproduction," he said.

[endofquote]