Unscrambling Diabetes - it's all about FAT

Lindsay Wu

One person every 10 minutes is being diagnosed with diabetes in Australia –
Will you be next?


HOW DO YOU STUDY DIABETES?
The highlight of my day on the 12th of April 2006 involved the optimization of an experiment that will assist in the isolation and identification of novel proteins involved in insulin signalling.

WHY AM I STUDYING PROTEINS AND INSULIN SIGNALING WHEN PEOPLE ARE DYING?
Improving our understanding of the underlying mechanism of insulin signalling and resistance of type 2 diabetes will allow us to create better diagnosis, better treatments and ultimately prevention of this costly and deadly disease.

MY BACKGROUND
I am currently completing a PhD in the field of biochemistry at the Garvan Institute of Medical Research. Our group is interested in the process of cellular glucose transport, in the context of type 2 diabetes.

WHAT IS TYPE 2 DIABETES ANYWAY?
Type 2 diabetes is a disorder of glucose metabolism. Normally when we eat a meal, food is broken down in the gut, and is released into the bloodstream. This rise in blood glucose levels is detected by the pancreas, which secretes an important hormone, insulin, into the bloodstream. Insulin circulates throughout the bloodstream, and interacts with fat, muscle, and the liver.

When insulin comes into contact with a muscle, fat or liver cell, it sets off an intracellular signalling pathway. One of the end results of this pathway is glucose transport - the cell sucks up glucose from the bloodstream, and lowers blood glucose. In type 2 diabetes, cells undergo “insulin resistance”, and despite coming into contact with insulin, some unknown defect in the intracellular signaling pathway blocks the signal that allows cells to suck up glucose.

WHATS SO INTERESTING ABOUT THE INTRACELLULAR SIGNALING PATHWAY?
This intracellular signalling pathway, which is thought to contain the defects that prevent cells from sucking up glucose from the bloodstream, is almost entirely composed of proteins that are able to “talk” to one another, by a chemical modification known as phosphorylation. Insulin signalling is an incredibly complex problem that involves dozens, perhaps hundreds of proteins, which “talk” to one another in different ways, under different conditions.

Understanding how each protein talks to other proteins is critical to understanding type 2 diabetes. If we are able to understand precisely how proteins within the cell “talk” to one another, then we should be able to understand where exactly the defect exists in diabetic cells, and have a chance at targeting these defective proteins for drug treatment.

THE "SCIENCE" BEHIND SOLVING THE PROBLEM

My project involves using a technique known as “mass spectrometry”, which allows identification of proteins by precisely measuring their molecular weight. Using this technique, I hope to isolate and identify all of the proteins that “talk” to one another in response to insulin.

My experiment on April the 12th was designed to increase the efficiency of isolation of these proteins that are found to be “talking” to one another in response to insulin. This experiment was essentially a sort of titration, based on the same concept as the acid/base titration all high school chemistry students are taught.

HOW I GOT INVOLVED IN RESEARCHING DIABETES
This is currently my first year of my PhD. I am currently enrolled through UNSW, however the vast majority of my work takes place at the Garvan Institute of Medical Research. The mass spectrometry part of my work takes place in the bioanalytical mass spectrometry unit at UNSW.

Last year, I completed my undergraduate studies. My undergrad degree was a Bachelor of Science (molecular biotechnology), with a major in biochemistry, followed up by first class honours in chemistry, from The University of Sydney. Honours was a great experience, I was given an expenses paid trip to the USA to do experiments using an x-ray beamline not available in Australia (but will be available in 2008). I completed some great research that will hopefully be published in the near future.

"A CAREER IN SCIENCE IS A GREAT WAY TO TRAVEL"
In the future, after my PhD, I aim to take up a position as a post-doctoral researcher in a couple of overseas positions. A career in science is a great way to travel, to further one’s career, working overseas is a must. Places available include the US, Europe, however Singapore and Hong Kong are fast emerging as centres of life science research.

MORE ON ME !!!
I chose to do science at the end of high school because I enjoyed biology and chemistry. I was motivated by medical research, and finding cures for human disease. Biotechnology is a rapidly growing field with applications that have the potential to improve life around the world. I like to think of getting into the field at the early stages as the equivalent of Bill Gates and his mates mucking around in their garage before the true power of computing kicked off the I.T. revolution.




Here's me playing with the end of a synchrotron beamline in the US.


Interesting links!

Diabetes Australia
www.diabetesaustralia.com.au

Australian Diabetes Society
www.racp.edu.au/ads

American Diabetes Association
www.diabetes.org

International Diabetes Federation
www.idf.org/home/

The World Health Organisation
www.who.int/en/

Written by Lindsay Wu - Edited by Catherine Beehag

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