A microbiologist from Melbourne who is removing genes from the malaria genome to work on a vaccine against the world’s most malignant parasite.
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Researching the biology of a single-cell parasite helps microbiologist Alex Maier appreciate the big picture.
"I'm intrigued by the fact that if we manipulate an organism on the molecular level then we can create impact on a population level. Vice versa, we introduce a science policy and by following it up, we can create evolutionary pressure to alter an organism - for example drug resistance."
Alex is leading work on a vaccine against the world's most malignant parasite, malaria, which causes nearly one million deaths each year. As a sign of its rampant spread, it is now estimated that as many as one in 14 people around the world have a red blood cell mutation that was caused by contact with the malaria parasite at some point in their ancestral history.
The Melbourne-based researcher removes (or "knocks-out") molecules from the parasite's genome. The function of a molecule is then deducted by comparing a parasite containing all molecules to a parasite missing the molecule. Knocking out one gene had previously been an incredibly laborious process of more than six-months, but Alex stunned the international research community by streamlining the process and being able to ‘knock out' or remove 83 genes from the parasite's genome. This tripled the amount of molecules analysed by this method worldwide.
By knocking these genes out, Alex has been able to work out what role they play within malaria. In this way he has identified 30 proteins or molecules produced by the single-celled organism, that are essential for the parasite's survival, helping protect it from the body's immune system.
"All the new knowledge we have acquired about those molecules allows us to delve deeper into the parasite and really prioritise the candidates we want to know more about.
"We want to understand the mechanisms of those molecules and by understanding them, it will allow us to come up with substances or methods to interfere with the function of those proteins."
Alex says his lab work needs to be complemented by continuing work on the ground to prevent mosquitoes biting people in the first place; and by the ongoing development of new medicines for treatment, in the face of increasing drug resistance. But his hope is that his research will soon lead to a situation where the body can be helped to be able to get rid of the parasite itself, with the aid of a vaccine - what Alex calls the "magic bullet".
In the meantime he spends as much time as he can sharing his excitement about science and the need for greater scientific literacy with Australian students of all ages.
"Science is very much a creative process and for me that's the exciting bit, you don't know where science actually leads you. You are an explorer there and you enter unknown territory.
"The skill you have to develop is to be flexible and respond to what the experiment delivers to you and hopefully be bright enough to realise when an opportunity is presented."
Alex Maier works at La Trobe University and entered his research in the Eureka Prize for Scientific Research. He was a finalist for the same award in 2010.
If you win, how will you use this advantage of winning to improve this science?
The intention of the Eureka Prizes is to raise public awareness. There is lots of terrific science done in Australia, but most of the time the results are only published in specialist journals. It is a great opportunity for scientists to showcase their work and for the public to see how some of their taxes are spent.
A disease like malaria has lots of social and economical consequences. Although it is one of the biggest killers in the world most people in Australia are relatively unaware of it. Being a People's Choice finalist has opened up many opportunities to promote the awareness for this disease already. A win would be a public endorsement of our research, open up even more possibilities for a dialogue with the public and might inspire other people.
How many people are affected by Malaria, and which countries can you get it?
Half of the world's population lives under the threat of malaria. Every year approximately 250 million people contract the disease (that's over 10 times more people than the population of Australia) and almost 1 million loose their lives due to malaria. To contract malaria several conditions have to be met:
- An Anopheles mosquito has to suck infected blood from a malaria patient
- The surrounding temperature has to be warm enough so that the malaria parasite can develop inside of the mosquito before the mosquito dies.
- Once the parasite has developed, the mosquito has to bite another human to transmit the disease.
The disease is most prevalent in Africa and South East Asia, but Australia's neighbouring countries like Papua New Guinea and Indonesia are affected. By the way, Australia was only declared malaria free in 1981 (but there are still several hundred cases of imported malaria each year) and for centuries malaria caused havoc in Europe.
What science degrees did you need to be where you are now?
Scientists work in teams. Scientific teams usually consist of different members: e.g. Honours and PhD students, research assistants, people with PhD degrees wanting to gain experience and team leaders. And as in team sports every position is crucial for the overall success. Team leaders normally hold a PhD degree. The training background of people working in Medical research varies: biochemists, microbiologists, cell biologists, geneticists, molecular biologists, zoologists, chemists, computer scientists, people with a medical degree... But all have a common passion, the desire to explore the unknown and the hope to make the world a better place.
Would this perhaps have a similar out come on other species etc such as horses or cows?
The knock-out technology can be applied to a lot of species. On a genetic basis mammals are quite similar and therefore very often results obtained for one species can be applied to other mammals as well.
The genetic make up of the malaria parasite on the other hand is quite different. This is great, since this is an opportunity to discover specific drug targets and new biological functions, but it requires identifying these functions first.
What technologies did you use to 'knock out' these genes?
You can imagine DNA as a street with gene locations as houses. Every gene "lives" at a certain location with a distinct address. To knock a gene out means to replace the current tenant of this location with another tenant (a gene for antibiotic resistance). We therefore add the address to the resistance gene and introduce it into the parasite. The parasite's own housekeeping mechanism ("the real estate agent") recognizes the address and exchanges the current tenant with the new tenant, which is the resistance gene.
This procedure is very inefficient and happens only in one out of millions of cells. The addition of antibiotics kills normal parasites, but the gene knock out cells contain the resistance gene and can survive in the presence of antibiotics. With this selection procedure we identify the knock-out cells.