Anticipating and countering infectious diseases

Climate change and economic development are, together, rapidly altering the ecological niches of thousands of “vector” species — organisms capable of carrying disease-causing bacteria, viruses, and parasites — which brings them into greater contact with humans. This increases our risk of being infected by parasites and harmful viruses and bacteria.

Unfortunately, existing lab models are of limited value in assessing where pathogens will spread and in evaluating their risk to humans. Researchers in the labs of Founding Member Rudolf Jaenisch and Institute Member Sebastian Lourido are helping overcome this limitation by leveraging expertise in stem-cell technology and in the host-pathogen interactions. “To begin, we are deriving new induced pluripotent stem cell lines from a variety of species that serve as virus and parasite vectors,” says Jaenisch, who is also professor of biology at MIT. “We use these cell lines to create in vitro organoids that mimic the tissues that are common sites of initial infection. These species-specific organoids are sustainable models for studying many kinds of infection in the lab.”

Lourido, who is also associate professor of biology at MIT, lays out the next step: “Our teams are developing pathogen-specific methods to infect the organoids; then observing the conditions that promote or limit the ability to actually infect them. This will meaningfully advance our capacity to evaluate each pathogen’s risk to humans.

“Ultimately,” Lourido explains, “we believe these organoids will become platforms for developing scalable technologies for assessing emerging threats and intervening in infectious disease outbreaks.”

The Jaenisch lab is also helping develop practical new ways to deal with widespread infections caused by tick- and mosquito-borne pathogens. One project — a collaboration with MIT Associate Professor Kevin Esvelt, who develops methods for introducing new biotechnologies safely — aims to prevent Lyme disease transmission by heritably immunizing local mouse populations against the disease-causing pathogen. (The mice are reservoirs of the pathogen; ticks bite the mice, then transfer it to humans). Working closely with two Massachusetts communities, the researchers are preparing a test-intervention: orchestrating release of immunized mice on the Lyme-infested islands of Nantucket and Martha's Vineyard, with the goal of replacing the existing mouse population with Lyme-resistant mice.

At the same time, Jaenisch’s team is working to understand exactly what happens when tick- and mosquito-borne viruses infect human cells. Working with Lee Gehrke, the Hermann L.F. von Helmholtz Professor at MIT, their studies will address mosquito-vectored viruses such as Zika, Dengue, and West Nile, and tick-vectored viruses such as Powassan, Deer Tick, Heartland, and Bunya. “We believe that knowledge gained through this project will better position translational scientists to rapidly develop methods to stop viruses from entering or replicating within human cells,” Jaenisch says.

Read more about the goals of — and some of the scientific projects comprising — the Whitehead Initiative on Biology, Health, and Climate Change.