Transcript

Treating Malaria on the molecular level

Alexander MaierAlexander Maier
Email: a.maier@latrobe.edu.au

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Matt Smith:

Welcome to the La Trobe University Podcast! I would be your host Matt Smith, and with me today is Dr. Alexander Maier from the Department of Chemistry at La Trobe University. He's the Head of the Maier Lab and he's recently been shortlisted for the Eureka Prize. Thank you for joining me, Dr. Maier!

Alexander Maier:

Thank you, Matt.

Matt Smith:

Now, your research has been centred on malaria. Can you put the malaria problem into perspective for me and what is it and what is it being caused by?

Alexander Maier:

Malaria is a huge problem in the world. Malaria is caused by a single-cell organism called Plasmodium. And those Plasmodium they are transmitted, as everyone knows, by mosquitoes. And once they are inside of the human host, they first go to the liver, develop there. And from the liver, the parasite spreads into the bloodstream where it infects human red blood cells.

Worldwide, approximately 40% of the people live under the threat of contracting malaria, which is a huge number. Several hundreds of millions of people per year get infected. And almost a million people die every year from contracting malaria. Most of them are pregnant women and kids under the age of five. As everyone knows, it's a disease very prevalent in the tropics, in the developing countries. But, what is not so much known is that it used to be very prevalent also in Europe and even in Scandinavian countries. So the last case of malaria in London was eradicated in the 1950s.

Matt Smith:

There's a common misconception that it is a virus. What exactly is it that's causing the problem?

Alexander Maier:

It's a unicellular organism, so it's a single cell. Quite similar to the cells that you and I have in our bodies. And that makes it also a problem in fighting it because it's so similar to our body, versus a virus looks quite different to what we find inside of our bodies. It then invades red blood cells and it uses the red blood cells more or less as a safe haven to be protected from our immune system.

However, being inside of the red blood cell comes at a price. It has to interact with the surrounding of the red blood cells. And therefore, it actually alters the red blood cell. The red blood cell as everyone knows has more defined function, carrying oxygen to our organs. However, once it's invaded by the malaria parasite, the function changes completely and it becomes a slave of the parasite. The parasite alters the protein composition inside of the red blood cells and also manages to export some of its proteins. We call that viral infectors.

So, those are actually factors that make us sick. So, the parasite actually transports those viral infectors into the red blood cells. And from there, on the surface of the red blood cell, they act as hooks to connect an infected red blood cell to the lining of blood vessels. This is important since the spleen can actually detect infected red blood cells and can put injury clear infected red blood cells from our bloodstream. However, since the infected red blood cells stick to blood vessels, they never reach the spleen. And therefore, the parasite can develop quite easily.

Matt Smith:

What work have you been undertaking to fight malaria?

Alexander Maier:

We are using a technique called the "knockout approach", where we actually delete information in the parasite so that certain proteins can't be made anymore. By deleting those proteins, we then want to find out what the function of those proteins is. Normally, if you have an organism, you will then compare those proteins to other organisms. And if a similar protein was described in the other organism, you can detect the functions from it. In the case of the malaria parasite, 60% of its genes don't show any similarity to other proteins in other organism. So, we are in complete darkness what the function of those proteins actually is.

If I may, I would like to compare that to an analogy. If you want to find out what the function of certain parts in a certain car is, and you remove the steering wheel, you will all of a sudden find out that the steering wheel is involved in the direction of the car. If you remove the motor, it can't drive and so on, and so forth. Pretty much that's what we do. We remove parts of the parasite. And then, from its deficit, what is missing in terms of function, we detect what the function of this protein is. However, this can very often be a challenge. If, for example, you remove the wipers of a car, you have to drive in rain to see that the wipers are actually important. Otherwise, you would never detect it. And this can be quite a challenge.

Matt Smith:

So, have you come up with any favourable results and have you knocked out anything that seems to be effective?

Alexander Maier:

In being able to find the function of the proteins in our "knockout approach", we created what we call a library of cells, which have different knockouts. In this library, we actually find a lot of proteins which are absolutely essential for the survival of those parasites. If you now interfere with the functions of those essential proteins, you have a track target. If you find a chemical which interferes with the functions of those proteins, that's your future track. In addition to it, we unravelled components of mechanisms, how those viral infectors actually become delivered to the surface of the red blood cell. Again, it's important to understand the mechanism before you can find an agent to interfere with it.

Matt Smith:

So, what exactly would a drug that interferes with it do? Would it just stop it from latching on to the red blood cell and make it useless as far as it would be flushed out to the spleen after that?

Alexander Maier:

Yes, exactly. We remove the possibility that those hooks can reach the surface of the red blood cell. And therefore, the infected red blood cell can't adhere to the blood vessels anymore, get flushed to the spleen and the body can actually get rid of the infected red blood cells. It might eventually have a beneficial effect for the body, that the body is actually getting rid of it itself, because by this mechanism, it could evoke a protective immune response. It won't be a 100% protective, like in vaccines, but it could help the body in fighting future infections.

Matt Smith:

And are you at this stage at where anything can be practically applied?

Alexander Maier:

It's early stages, but the malaria parasite is an absolute wonder to me. It's a single-cell organism and it's known for thousands of years, however it still outsmarted us. And it beats all of the billions of cells in our brain, just by the poor mass of it. We have to remember that of every infected red blood cells, after 48 hours there will be 32 new parasites coming out. And four days later, it will be 124. And actually, 12 days later it will reach over a billion parasites, deriving from one single parasite.

Matt Smith:

Do you think that science will reach a stage where there's a cure for malaria? Or will this always be an ongoing challenge?

Alexander Maier:

Very often with infectious diseases it's never a standstill. It's always an arms battle. We have effective drugs against malaria. That's not the problem. The problem is the track resistance which actually occurs and leaves one successful tracks absolutely useless. So, we have to have enough new drugs in the pipeline, in order to combat the disease.

The other thing is, also, additional level of complexity is the fact that this is a disease mainly in poor countries. And very often those countries have a health budget of two dollars per year per person. If you have a drug which is five dollars a pill and you have to take a pill everyday, that's absolutely useless just for one disease. So, it must be incredibly cheap. It must be very effective. The mode of…Administering it must be ultimately easy.

Matt Smith:

You were originally from Germany, what brought you to Australia to conduct your research?

Alexander Maier:

I was always fascinated by parasites. And I did my PhD on another parasite. And I wanted to stay in parasitology. And malaria is clearly one of the biggest parasitological problems in the world. Melbourne is almost a world capital in malaria research. So many good groups in Melbourne, so many world-class groups, that it was just a logical choice, if you want to work in malaria, to get education in Melbourne and then apply in other countries. I like Australia that's why I stayed in Australia.

Matt Smith:

That's kind of true. Here at La Trobe we've got yourself, we've got Leann Tilley who's working on malaria, Mick Foley working on using shot gun to combat malaria, and Professor Robin Anders. Do you have a kind of betting pool? Who's got the best odds at the moment? Is this Eureka Prize going to help you get a betting pool at all?

Alexander Maier:

It's certainly a great honour, but the times of Alexander Fleming's are over. Science is very much team sports nowadays. And it takes a lot of people to be successful and probably, it takes only one person to ruin it. So, that's another thing about the malaria community in Australia. Everyone is very generous. Everyone is very supportive. Ideas and reagents flow quite freely between the different groups. And I think that's absolutely a strength of the malaria community in Australia.

Matt Smith:

Dr. Alexander Maier, thank you for your time today.

Alexander Maier:

Thank you very much.