Julian Rayner

Malaria Research: Red Blood Cell Invasion

Julian leads a research group that investigates the interactions between humans and the parasite that causes malaria. He focuses on how the malaria parasite, Plasmodium falciparum, recognizes and invades human red blood cells. Red blood cell invasion is a largely unexplained biological process that is essential for parasite development, and leads directly to the symptoms and pathology of malaria. His research uses techniques to look at genomes (all the genes present on the parasite’s chromosomes) and proteomes (all the proteins expressed by a genome) to understand how red blood cell invasion happens at the level of individual proteins. This research may lead to new biological insights and improved strategies for preventing and treating malaria.

Julian graduated from Lincoln University in New Zealand in 1993 with a degree in Biochemistry. He then moved to the UK to work as a graduate student in Dr Hugh Pelham’s lab at the MRC Laboratory of Molecular Biology in Cambridge. In Hugh's lab, Julian worked on yeast looking at how proteins are displayed on the outside of cells and received his PhD from the University of Cambridge in 1998.

When looking for a new research field to study as a post-doc, Julian stumbled across a review written by Dr John Barnwell describing what was then known about how the malaria parasite invades human red blood cells. The combination of fascinating biology with a disease that leads to more than a million deaths each year caught Julian’s interest, and he was hooked. From 1998 to 2002 he studied as a post-doctoral research fellow in John Barnwell's lab at the Centers for Disease Control and Prevention in Atlanta. Here he helped identify and characterise a new family of P. falciparum proteins involved in recognising human red blood cells. In 2002, Julian became a faculty member in the Department of Medicine at the University of Alabama at Birmingham, where his team worked on the molecular details of how P. falciparum parasites force their way inside red blood cells. During this time he also established strong links to field studies in areas affected by malaria, such as the Peruvian Amazon.

Julian joined the Wellcome Trust Sanger Institute's Malaria Programme in 2008. The Sanger Institute’s Malaria Programme uses genomic, genetic and proteomic approaches to discover molecular mechanisms of host-parasite interactions.


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My research
Julian Rayner 0:44 min - 4584 kb
I’m Julian Rayner, so I work on malaria parasites trying to understand how they invade red blood cells and how they make people sick. We work on the parasite in the lab, so we actually grow the parasite inside human red blood cells in the lab and that means we can follow it through microscopy and through various molecular biology techniques, so we can knock genes out, we can put genes in, we can try and understand the fundamental biology of how the parasite recognises red blood cells and gets inside them and by doing that we hope to come up with ways to interfere with it, either to develop a vaccine to prevent it or to develop drugs to kill it after its inside the red blood cell.
Overview of malaria and the lifecycle of Plasmodium falciparum
Julian Rayner 1:50 min - 11,527 kb
So malaria is a disease that's caused by parasites and there are several different parasites that can cause malaria in humans and in fact malaria is a very common disease of a lot of animals, so monkeys get malaria, apes get malaria, birds get malaria. They are all caused by parasites of the Plasmodium genus, so Plasmodium falciparum, Plasmodium vivax, several other Plasmodium species, so there are four species of Plasmodium that infect us routinely and the parasite cycles back and forward between humans and mosquitoes. So we don’t pass it from people to people, it goes from us to a mosquito and then to another person. So when the mosquito first bites you and infects you, the parasite first goes to your liver and develops inside your liver for a week or two and you have no symptoms and no pathology and you don’t know you’ve got it and then it comes out of your liver and into your blood and that’s the stage that causes all the symptoms and its also a derivative at that stage that then gets picked up by another mosquito, so then another mosquito bites you and transmits you to something else. The disease is actually caused when the parasite is inside your red blood cells. So there are a couple of different stages inside your body but the one that makes you sick is when the parasite invades your red blood cells, multiplies inside them and then it just blows the red blood cells up and infects new red blood cells, so you can imagine it just churns its way through your red blood cells, you get severe anaemia, you don’t have enough red blood cells to carry oxygen around your body, you can get some pulmonary distress, you’re not transporting oxygen efficiently and then there are various other complications including coma, kidney complications, and in pregnant women complications in the placenta that affect the developing foetus.
Developing immunity to malaria
Julian Rayner 1:21 min - 8,463 kb
If you grow up in a very heavily malaria endemic area where you’re getting infected a lot, you develop immunity. So over a long period of time you develop protection against malaria. It’s an interesting kind of immunity though, if you went to a village in a high transmission region of say Kenya, and sampled all the adults in that village, maybe 75% of them would have parasites in their blood stream at any one time, they just wouldn’t get very sick. So you can develop immunity to severe malaria, to Plasmodium falciparum malaria, but it takes quite a long time to do it and so that’s why children are the ones who tend to die. It's because they have not yet developed that immunity. So past the age of five or six or so, the rates, the death rates start to go down dramatically, they have developed immunity and that fact, the fact that you can develop immunity to malaria, is the reason that gives us hope that we should be able to develop a vaccine, so if your immune system can do it, we as scientists should be able to do it, we just haven’t worked out a way to do it yet and its a very hard problem, there is no vaccine against any parasitic disease, so this would be the first, but there is no vaccine yet.
 The challenges for developing a vaccine for malaria
Julian Rayner 1:12 min - 7,564 kb
Vaccines is a completely different problem, so the problem with vaccines is two fold. One is the parasite is just really smart. So remember the parasite invades red blood cells, it hides out inside a human cell, so it protects itself from the immune system. There are some tweaks to that, it's vulnerable in other ways but a lot of the time it is just protected and it's only outside as a free living organism for a very short period of time, it can't multiply outside a human cell. That’s the first problem. So you've got a very brief window of time, for say antibodies, to try and attack it. The other problem is, it’s a complex eukaryotic cell, so that means it’s a complicated cell in the same, of a similar kind to human cells or plant cells. It has more genes, it undergoes sexual recombination, it shuffles genes. So what that means is that genes can be very variable between different parasites and the challenge is to come up with a vaccine that protects across lots of different genetic variants. It's not as simple problem by any means.
The most interesting part my work
Julian Rayner 0:46 min - 4,862 kb
The most interesting aspect from a pure scientific point of view, I think, comes down to this process of one cell getting inside another cell. How does that happen? How does one cell bind to another and drive its way in, because its all an active process, its driven by the parasite. The red blood cell is sort of an innocent bystander, just getting invaded by the parasite. So how does that work on a molecular mechanism? What are the proteins that interact with each other? How does that translate into force? How is that regulated? How is it switched on and off? How does it vary from one person to another person? Those sorts of questions, I think are the most, to me, fascinating biological questions there are.
Malaria research at the Sanger Institute
Julian Rayner 1:48 min - 11,294 kb
We work at several different levels in reality, there is a group of people who works directly with me and those would be PhD students and postdoctoral scientists and technicians and people at a range of different training stages in the scientific process and they work on experiments in my lab directed by me. But then we also have many levels of interactions with other groups, both here at the Sanger Institute and also around the world. So at the Sanger we’re lucky enough to have several groups, all are working on malaria, all working in slightly different ways and stages. So we have a big group that’s interested in natural genetic variations, so between different parasite isolates, so they can do a lot of investigation of the natural genetic variation. We can look at the impact of some of that variation on the behaviours, the phenotypes that interest us, red blood cell invasion. We have other groups who are interested in the mosquito stages. What does that parasite do inside the mosquito after it gets taken up in a blood meal and there are some things that happen there that are actually very similar to the things that happen in the red blood cell stages, so we can compare and contrast. So there is that level of interaction with groups here at the Institute, but then malaria by definition is a big community of people working together and we are very reliant on people working in the field, working with clinical samples. Because when it boils down to it, what we are interested in is solving a clinical problem, so we have to have that layer of people who understand the clinical implications, the pathology, how things work in the field. So there are all those levels of interactions that we handle on a day to day basis.
The most important aspect of my work
Julian Rayner 1:24 min - 8,796 kb
So I think the most important aspect of my work is that we’re working on a disease that affects people who are in difficult economic circumstances. So it’s a disease that’s not of high priority to big pharmaceutical companies, it’s a disease that is not necessarily of high priority to governments in the western world and so it really feels like a communal and community effort by researchers both here and in Africa and all across the world, trying to do something for the common good. So the most important aspect to me is that sort of collegial, community effort. In reality, the chances of me individually designing the vaccine that will cure malaria are very slim but the reality is we are all contributing to a great pool of knowledge and out of that pool of knowledge, something really fundamentally good for humanity will come and so that’s the most exciting and important aspect to me.