Schistosomiasis: what happened next?

15 June 2017

Interview with

Jim Collins, University of Texas Southwestern Medical Center

Last year the Naked Scientists heard from Jim Collins at the University of Texas Southwestern Medical Center. He’s been studying schistosomes, and when we last spoke he’d just discovered one of the ways that these parasites, which multiply inside freshwater snails and then infect humans when they enter the water, fend off our immune response. Chris Smith caught up with him to hear how the work’s progressed…

Jim - Schistosomes which are these parasitic flatworms infect hundreds and millions of people have stem cells. Once they're inside their human host, they're capable of surviving there for decades. We’ve postulated that the stem cells are playing an important role in keeping their tissues young and healthy throughout this really long lifespan that they have.

Chris - Because one of the big challenges is, these parasites have to live up-close and personal with the immune system, and they're therefore potentially being attacked and assailed all the time, aren't they? So they may well have tissues that need replacing.

Jim - Exactly. So they live in the blood which is basically the frontlines of the immune system. And so, what we found is that these schistosomes – the so-called blood flukes – they have these stem cells but it seems that the main job of these stem cells in the parasite is to constantly rejuvenate the parasite’s skin which is the structure called tegument. And so, it suggests that stem cells are playing a role in perhaps allowing the parasite to maybe even to survive in the blood, but maybe also as a means that they were able to invade the host immunity.

Chris - Now that’s sort of where we left off when we spoke last time, but how have you taken the story forward and actually, challenged that notion to say, “Well, if that’s true, we’d better prove it.”

Jim - So it turns out that that’s a very challenging experiment to do – to directly test the model that the stem cells were involved in modulating how the parasite interphases with the host. And so, what we’ve been focusing on is the developmental aspects of how the stem cells are rejuvenating this tegumental structure.

Chris - Presumably, if you were to disable this system then you would render these animals much more vulnerable to things like immune attack. And therefore, the likelihood of them being cleared from the body would go up enormously.

Jim - Exactly. So, if we could figure out a way to block the stem cells’ ability to make these tegumental cells, then that absolutely could be a way to think about trying to target these parasites. If you blunt their ability to make new tegumental cells, our hypothesis is that then the parasites would no longer be able to survive the hostile environment within the immune system and those are experiments that we're actively trying to get to work in the lab. It turns out it’s not such an easy experiment because what it actually requires is a viable immune system which we have really no means of replicating inside of a dish where we, in cell culture where we do a lot of these experiments to the parasites, what's it going to require is taking parasites out of a host such as a mouse, manipulating them to deplete their stem cells and then transplanting them surgically back into an animal that’s capable of evoking immune response against the parasites. And so, we’ve developed a procedure based on Pplusic literature to be able to do this in the lab. We successfully done that and so now, we’re working to basically kill the stem cells and then put the parasites back in and see what happens.

Chris - Is there no way you could wire some kind of genetic vulnerability into the cells so that you could for instance administer a drug and then kill them off that way?

Jim - Yeah. It’s one of the challenges of studying – when we collected tropical disease is that in many ways, the organisms that we use had experimental neglected and we don’t necessarily have the tools that you have to study things like fruit flies or nematodes. And so, one kind of pie in the sky idea that a number of people in the community are trying to develop is genome editing techniques where you basically use this system called CRISPR/Cas9 to make changes of the genome in the organism and then you can exploit those to try to understand the biology of the animal. Unfortunately, given the way that parasites live, they have a very complicated life cycle. It makes it really challenging to try to develop ways to implement this kind of new genome editing technologies to manipulate these parasites.

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