A disease of global significance
S. mansoni spends most of its life inside either a snail host or a mammalian one and has two short-lived larval stages, where it lives in freshwater. Inside a human host, adults roughly a centimeter long survive in the blood vessels lining the intestines, laying hundreds of eggs per day鈥攕ometimes for up to a decade or more.
MBLhalf of these eggs are excreted in feces, Rawlinson said, but the other half get lodged in tissues and organs such as the liver. The human immune system reacts defensively, encapsulating the foreign eggs inside structures called granulomas.
鈥淎nd the more eggs, the more encapsulated structures are found in our liver, which makes the organ hard,鈥 Rawlinson said. 鈥淎nd it means that our liver function goes down. We've got this really hard liver that's not functioning properly, and that's what causes a lot of the pathology in the disease.鈥
WHO recommends praziquantel for prevention and treatment of the disease; though the drug is safe, effective, and low-cost, it has limited availability, the organization says.
Combining years lost to premature death and years lived with a disability, schistosomiasis is responsible for 2.6 million years of lost health, Rawlinson鈥檚 lab says. In 2021, WHO adopted a road map on neglected tropical diseases that set out to eliminate schistosomiasis as a public health problem in endemic countries by 2030.
鈥淚t's a really nasty parasite,鈥 Rawlinson said. 鈥淎n important parasite.鈥
Building a cell atlas
To build the cell catalog, or atlas, Rawlinson and Attenborough first harvest cercariae from infected snails. They collect and isolate individual cells from the cercariae and use a technique called single-cell RNA sequencing to determine which genes are being expressed鈥攐r switched on鈥攊n specific cells.
Attenborough then uses software programs to group the cells together based on the similarity of their gene expression. If a specific gene is only switched on in certain cells, those cells are likely the same type.
Once they鈥檝e found genes characteristic of certain cell types, Rawlinson and Attenborough use an imaging technique called in situ hybridization to visualize where those genes are being expressed in cercariae鈥攁nd as such, where those cell types are located within the worm.
鈥淲e're at the stage now where we can look at this multicellular parasite at a resolution that has never been looked at before,鈥 Rawlinson said. 鈥淲e can dissociate the cercariae into a soup of its own cells, sequence the RNA from each cell, group these cells computationally based on their gene expression, identify genes that represent each cell type and look at where they are expressed in the animal. This gives us information about the cell and tissue architecture of the larva and also helps us understand the function of different cell types, for example, whether a neuron might be sensory or motor.鈥