Episode Summary

Dr. Michael Ginger, Dean of the School of Applied Sciences in the Department of Biological and Geographical Science at the University of Huddersfield, in West Yorkshire, England, discusses the atypical metabolism and evolutionary cell biology of parasitic and free-living protists, including Leishmania, Naegleria and even euglinids.
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Ashley's Biggest Takeaways

  • Parasites demonstrate many unique biologic and metabolic properties.
  • These organisms are incredibly adaptable, often with multiple lifecycles and the ability to move from one vector to another.
  • Each new host presents a unique biochemistry, along with other environmental factors, for the parasite to navigate. 
  • Understanding parasite biology—metabolism in particular—may present opportunity to develop new medicines.
  • Understanding the complexities of parasite metabolism may also have important applications for  bioremediation of environmental pollutants, like phosphate. 

Featured Quotes:

Well, you're talking about organisms that have evolved to live very set life cycles, often involving more than just the host in which they're going to cause disease. There might be vectors that are involved in the transmission of a parasite from host-to-host. And here we're talking about life in the vector involving movement of the parasite from one part of the vector to another part of the vector—very different environments within the vector. And to move from A to B, maybe via C and D, that parasite is going to differentiate into new forms in which the morphology and the biochemistry are going to differ. 

In terms of what makes parasite metabolism unique, I guess, the paradigm that I grew up on, and many people grew up on, was the idea that a parasite becomes evolved or entrained to obligate parasitism, so it throws away the metabolism that it no longer needs. And that's part of what locks you into obligate parasitism. 

Over the last 10 years or so, at least for 2 major groups of parasites, the trypanosomatid parasites, and the apicomplexans, which include toxoplasma and malaria parasites, that paradigm has been sort of turned on its head a little. Whereas we did think that parasites evolved by throwing away metabolism—and that can be true—often, those bits of metabolism that are lost in the parasite are also missing from the free-living ancestors or the closest of the existing free-living ancestors to those parasites. We think now really, that it's perhaps both the characteristics that lock you into that obligate parasitic lifecycle.

"Making Good on" Parasite Metabolism for Translational Applications 

There's 2 ways to look at it. There's the sort of fundamental view of interesting evolutionary biology, and then there's biology that you can make good on in a translational sense—from a new medicine development perspective. Because we're talking about parasites that often cause serious diseases and diseases where there is a need for new medicines.

Often it's the surfaces of the parasites, and the way that they evolve to interact with host environment or vector environment, [that make them good parasites]. It's the evolution of surfaces that allow parasites to evade host immune systems, maybe manipulate host immune systems, talk to host cells and gain entry to host cells.

We work on a family of parasites called the trypanosomatids. They cause a variety of serious diseases in people. So you've got Trypanosoma brucei, which causes African sleeping sickness. You have Trypanosoma cruzi, which causes American trypanosomiasis through Latin America. Don't be confused by the same genus name there, T. brucei and T. cruzi. These are very different parasites in terms of many aspects of their biology.

And then we've we've got we've got Leishmania parasites, which cause a variety of visceral or ulcerating diseases in different parts of the tropics and subtropics.

I started my career working on the biosynthesis of sterols. In terms of what sterols do. They're components within eukaryotic cell membranes, and they influence membrane fluidity. They can also influence the types of proteins that accumulate in particular regions of the membrane.

So trypanosomatid parasites, they make ergosterol-type sterols that fungi make. They also scavenge a little bit of cholesterol from the human host, as well, or the animal host. The interesting feature here is that, in a general sense, the ergosterol steroids that they make, they make using enzymes that are often similar in biochemical terms to those yeast enzymes. Which means, in turn, although we make steroids—the cholesterol-type sterols—the enzymes that carry out similar or analogous reactions in our cells are less susceptible to some inhibitors than you would see in the fungal system, and, in turn, that you would see in the trypanosomatid system. And here the relevance is that many of the fungicides still in use are inhibitors of the sterole biosynthetic pathway. So, in a broad sense, this is a targetable pathway.

Bioremediation Applications for Environmental Polutants

We work in a very compact school in the school of applied sciences. So the biologists are on the same corridor, sometimes in shared office, with the chemists as well. And here we're talking about work that I'm involved in with a close collaborator and friend, Professor Craig Rice, at the University of Huddersfield

And he would often say that chemists make molecules. But if we can find biological application for those molecules, then we're potentially hitting the jackpot.

And that's what we're trying to do there. He's got a long standing interest in making what are known as self-assembling cryptand. And they, for all intents and purposes, make a cage that can capture molecules, and the types of molecules that Craig and his team are interested in are anions. So from an environmental perspective, we're talking about maybe the capture of phosphate. If we think about phosphate as a principal component in fertilizers, there are many freshwater environments in which phosphate is in excess, and that causes the problem of eutrophication. So, can you use the cryptands in any way to strip out phosphate from a polluted environment?

So Craig and his team, they make the ligand that can associate with metals to self assemble into cryptands that can capture anions. What do we do? We use those cryptands to take culture media and deplete them of phosphate, and we can use mass spectrometry techniques to determine the extent of phosphate removal. And then we can take the treated media, and we can ask how to well protests now grow.

Obviously phosphate is an essential nutrient for our cultures. In the case of eutrophication, then phosphate in excess, or phosphate and nitrate in excess, can cause problems. Too little phosphate, you don't see any growth in our laboratory systems, but at least you can add the phosphate back in.

What makes [collaboration] happen is it's meeting people who are different to yourself and just starting a conversation.

Looking at the biology and biochemistry of parasites is fascinating. It's kept me interested for for over 20 years, it's kept many other people interested for far longer. But you're not necessarily talking about the easiest microbial eukaryotes to work with.

For me now, the day job is mostly administration, some teaching. So we hope to be able to keep moving forwards as we have done deciding on the questions that we think we can answer. And then it's making good on the the huge amount of publicly available genome sequencing data, and coupling that to some of the biochemistry and cell biology that served us well over the last years.

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Michael Ginger