ARGHHHH! Run for the hills, it's a Helminth!

We had talks about scabies in the Aboriginal population, the mites that spread the disease, and I interviewed Dr Alex Loukas, parasitologist from the Queensland Institute for Medical Research. Dr Loukas has an interest in a member of the Helminth family the hookworm, and is currently working on developing a vaccine against the infection.

Hookworms are no longer a big problem for humans in Australia, but remain a health risk in the developing world. The manifestation of a serious hookworm infection is anaemia from a loss of blood, corresponding with low levels of iron.

Like the malaria parasite I wrote about in my previous post, hookworms consume the haemoglobin component of blood and they do this by latching onto the walls of the intestine and leeching blood into their gut. They then excrete the left overs out through their anus.

Which brings me to the pornography part of Alex’s talk yesterday. He has a video taken during a routine colonoscopy (which failed to work during the presentation and I can’t say that I am really sorry) showing a dog hookworm attached to the inside of a human patient’s intestine. According to Alex, it precisely demonstrates this process.

He refers to it as “pornography for parasitologists”. And people say scientists are weird.

But seriously, the main focus of Alex’s work is to develop a vaccine for hookworm. This might sound a bit strange to you at first, since many of us would know that there is already one available for dogs. Alex told me however that this vaccine, whilst a viable technology to adapt for human use, is far too expensive to use in the developing world. This is because it is an “attenuated vaccine”, meaning the hookworm larvae are irradiated to a senescent or no longer active state, then when the immune system is exposed to them, antibodies are created and immunity developed. This is a very expensive process however, requiring the culturing of hundreds of thousands of hookworm larvae for vaccine manufacture. Cost is a critical factor for the availability and distribution of medical care in the developing world.

Parasitology - it's fun.

To overcome these issues, Alex’s approach is to create an antibody against a protein in the feed cycle of the hookworm. This enzyme is critical for the final stages of the digestion of the haemaoglobin component of the blood. If the enzyme doesn’t work, the hookworm cannot extract nutrients and it effectively starves to death.

The method of delivery of the antibody to the gut of the worm is particularly fascinating. The host, being the human, is exposed to the hookworm gut protein, thereby making antibodies against it, which will enter their blood stream. The hookworm then feeds on the blood, ingests the antibodies which enter its gut and stop the digestive enzymes from working. Alex refers to this as the “Poison Chalice” of vaccines. Elegant and ingenious.

To hear the full interview with Alex Loukas, tune into the Skeptic Zone , episode 56, on November 13, 2009. Find us on iTunes.

See an alternative image of a hookworm eating its prey here.

To be more precise, the 6th General Meeting of the International Proteolysis Society held at the Marriot Hotel in Surfers Paradise. As one can expect in Queensland at this time of year, the weather is warm and very humid (read: lovely). We arrived at the end of a weekend of street car racing, so much of the centre of town is still cordoned off with barriers, fences and large signs for beer companies. Evidence of a recent bogan invasion is rife.

Poolside at the Marriot Hotel, Surfers Paradise. The famous natural reef complete with tropical fish.

Many of the conference delegates are clearly excited to be in such a location, one even stating that it is proof that “proteolysis takes you to paradise!” Suffice to say, there is a definite tropical/resort atmosphere and attitude permeating proceedings.

Science is hard (*does a little jig*)

However, we must not forget this is about the science, and in particular, proteases.

What are proteases?

Essentially they are enzymes, (like the ones you may have heard about on television commercials for washing powder), which are responsible for chewing up and recycling proteins.

If you remember back to high school genetics, you would recall that DNA, which is made up of hundreds of thousands of genes, (about twenty three thousand in the case of the human genome) holds the code for all our proteins. Enzymes are a class of these proteins, assigned many and varied tasks, such as protecting our cells from stress, helping to protect our DNA from damage and recycling damaged proteins.

The proteases (which are also enzymes) have varied roles including turning other proteins on and off and helping our cells to reproduce. But, like many functions in the human body such as the immune system, sometimes things can go wrong and instead of being useful, become toxic and cause harm.

Although we need proteases to survive, they can also contribute to illnesses such as cancer. One particular type of protease known as “cathepsin S” on one hand, helps our immune system fight invading pathogens, but on the other, has been shown to assist in the spread of cancer.

And humans are not the only ones who need proteases to survive. Parasites such a malaria and hookworm (a member of the Helmith family) need them to extract energy from their food. And in the case of these critters, human blood is what they love!

What about Malaria?

Malaria remains a huge global health crisis; 1 child dies every 5 seconds, there are 5 million cases every year of which 2 million die and a further 3 billion people are at risk of infection. The majority of these people are in the developing world and many are children less than 5 years old.

Dr McGowan at work.

Dr Sheena McGowan is a structural biologist from Monash University in Melbourne who has been studying the proteases of the malarial parasite in a search for new drugs. Her approach focuses on the feeding cycle of the malarial parasite which involves invading red blood cells and feeding on the haemoglobin by breaking it down into single elements. This “breaking down” process requires a protease, and Sheena has figured out if she can block the function of the protease, she could effectively starve the parasite.

In collaboration with a large group of scientists from all across the world, Dr McGowan has been able to determine the precise structure of the malarial protease, using an approach known as X-ray crystallography (see below). This is a very complex and difficult process, but in principle, by obtaining crystals of the protease and firing X-ray beams at it, scientists can work out the shape and precise structure. This information then allows Sheena and her team to design compounds that will block it from working. A bit like putting a key in to a lock, but coating it with superglue first, so that it sticks really tight and never comes out.

The crystal structure of the malarial digestion enzyme. The drug that may be able to inhibit it ("the key") is shown in magenta.

Dr McGowan’s work will help address the burgeoning problem of malarial infection in the developing world, especially in places where severity of the infection is exacerbated by co-infection with other infectious diseases such as HIV or tuberculosis.

In the meantime there is some good news on the malaria front, with a scheduled roll out of a vaccine across Africa in 2010. But, Dr McGowan is cautious to remind us that this will not be the end of the malaria scourge.

Unfortunately, parasites are clever little buggers, rapidly evolving ways to get around our drugs. This is why work like that of Dr McGowan and her team is so important in tackling new and innovative methods to design new drugs against infectious diseases.