Thursday, February 13, 2020

Spillover: Why germs jump species from animals to people

"Whenever you have novel interactions with a diverse range of species in one place you can have a spillover event," says Thomas Gillespie, an Emory disease ecologist.

When a disease spreads from one species to another it is known as a “spillover event.” Although not yet confirmed, preliminary evidence suggests that the virus that causes COVID-19, the 2019 coronavirus disease, may have originated in horseshoe bats in China. It may have spread to another species which in turn infected humans at a Wuhan live animal market, or “wet market.”

Thomas Gillespie, associate professor in Emory University’s Department of Environmental Sciences, and Rollins School of Public Health, is a disease ecologist who studies how germs jump between wild animals, domesticated animals and people. Through this “One Health” approach, he aims to protect humans, ecosystems and biodiversity.

Most of Gillespie’s research is focused in Africa and Latin America where his team is characterizing the diversity of new viruses and other pathogens in tropical forests. In the following interview, Gillespie explains how shrinking natural habitats and changing human and animal behaviors can add to the risks of spillover events.

Bats are linked to outbreaks of Hendra, Marburg and Nipah viruses, the Ebola virus outbreak in West Africa in 2014 and the SARS virus outbreak in China in 2002. Why do bats keep cropping up as prime suspects? 

One quarter of mammal species overall are bats. And in tropical systems, bats make up 50 percent of the mammalian diversity. Most bats feed on insects or fruit, but there’s a huge range of bat behaviors. There are bats that eat other bats, bats that eat fish and bats that drink blood. We are still discovering new species of bats. And each of these myriad bat species carries a suite of different pathogens. Bats are able to host different viruses without getting sick.

So bats, and the pathogens that bats carry, are numerous. And bats and humans are both mammals. This relatedness means we’re more likely to get a pathogen from a bat than from a cricket, for instance.

Some evidence suggests the virus that causes COVID-19 may have originated in horseshoe bats. (Getty Images)

Why are wet markets hot spots for disease spillover? 

Wet markets bring together a really broad range of animal species from different parts of the world. These animals are not eating what they would normally eat in the wild. They are stressed, which lowers their immunity and makes them more susceptible to pathogens. They are kept in cages where they are defecating on one another and, perhaps, through the cages onto other species of animals. They are also being butchered at the markets. Cutting up an animal and getting its blood on you is a good way to get a pathogen. All these factors make wet markets a perfect storm for cross-species transmission.

Whenever you have novel interactions with a diverse range of species in one place — whether that’s in a natural environment like a tropical forest or in an artificially created environment like a wet market — you can have a spillover event.

How are land use changes driving spillover? 

Major landscape changes are causing wildlife to lose habitats, which means more species may become crowded together while also coming into closer contact with humans. We see this in the United States, where suburbs fragmenting forests raise the risk of humans catching Lyme disease. Altering the ecosystem affects the complex cycle of the Lyme pathogen, which involves ticks, mice and deer. And people living close by are more likely to get bitten by a tick carrying Lyme bacteria. 

Logging and subsistence agriculture in Africa are reducing habitat for wild primates. They have less forest to forage in. That can make them unhealthy and more susceptible to disease. And it may drive them to risk encounters with humans, raising risks of the exchange of pathogens. In Uganda, for instance, crop raiding by red-tailed guenon monkeys led farmers to put cattle feces on their corn to make it less attractive to the monkeys.

And everyone is talking about the problem of the wet market in Wuhan, but what about the effects of the nearby Three Gorges Dam project? It is the world’s largest hydroelectric power station, built on the Yangtze River in an area that was previously a mix of secondary forest and agricultural land. Many of the animals that used to live in that area likely died when their habitat was destroyed, but bats can fly. Where did they go? How did they adapt?

How does your research address these kinds of problems? 

Most people don’t realize that we haven’t yet catalogued the full diversity of life, everything from viruses to mammals. At the same time, we need to understand more about how changing landscapes and novel interactions between humans and other species influence spillover. Why has one pathogen jumped across species while another one hasn’t? It’s important to gather data so we can use it to identify potential hot spots and risky behaviors. That may help us reduce the number of major spillover events, saving lives and preventing enormous economic losses.

Follow Thomas Gillespie on Twitter: @BiodiversHealth

Ebola's backstory: How germs jump species
Ecosystems hanging by a thread
Experts warn of pending extinction of many of the world's primates
In Madagascar, a health crisis of people and their ecosystem

Tuesday, February 11, 2020

New synthesis methods enhance 3D chemical space for drug discovery

Graphic shows the dirhodium catalyst developed to synthesize a 3D scaffold of keen interest to the pharmaceutical industry. The Davies lab has published a series of major papers on dirhodium catalysts that selectively funcitonalized C-H bonds in a streamlined manner.

By Carol Clark

After helping develop a new approach for organic synthesis — carbon-hydrogen functionalization — scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work — a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

“Our tools open up whole new chemical space for potential drug targets,” says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Davies is the founding director of the National Science Foundation’s Center for Selective C-H Functionalization, a consortium based at Emory and encompassing 15 major research universities from across the country as well as industrial partners.

Traditionally, organic chemistry has focused on the division between reactive molecular bonds and the inert bonds between carbon-carbon (C-C) and carbon-hydrogen (C-H). The inert bonds provide a strong, stable scaffold for performing chemical synthesis with the reactive groups. C-H functionalization flips this model on its head, making C-H bonds become the reactive sites.

The aim is to efficiently transform simple, abundant molecules into much more complex, value-added molecules. Functionalizing C-H bonds opens new chemical pathways for the synthesis of fine chemicals — pathways that are more direct, less costly and generate less chemical waste.

The Davies lab has published a series of major papers on dirhodium catalysts that selectively functionalize C-H bonds in a streamlined manner.

The current paper demonstrates the power of a dirhodium catalyst to efficiently synthesize a bioisostere of a benzene ring. A benzene ring is a two-dimensional (2D) molecule and a common motif in drug candidates. The bioisostere has similar biologicial properties to a benzene ring. It is a different chemical entity, however, with a 3D structure, which opens up new chemical territory for drug discovery.

Previous attempts to exploit this bioisostere for biomedical research have been hampered by the delicate nature of the structure and the limited ways to make them. “Traditional chemistry is too harsh and causes the system to fragment,” Davies explains. “Our method allows us to easily achieve a reaction on a C-H bond of this bioisostere in a way that does not destroy the scaffold. We can do chemistry that no one else can do and generate new, and more elaborate, derivatives containing this promising bioisostere.”

The paper serves as proof of principle that bioisosteres can serve as fundamental building blocks to generate an expanded range of chemical entities. “It’s like getting a new Lego shape in your kit,” Davies says. “The more Lego shapes you have, the more new and different structures you can build.” 

Zachary Garlets, a former member of the Davies lab who currently works for the biopharmaceutical firm Bristol-Myers Squibb, is first author of the paper. The project was a collaboration between the Davies lab and computational chemists from UCLA (Jacob Sanders and K.N. Houk) and medicinal chemists from Novartis Institutes for Biomedical Research (Hasnain Malik and Christian Gampe). 

The paper follows another recent demonstration of the potential for generating novel scaffolds relevant to pharmaceutical research using the method. That work, a collaboration between Emory chemists and AbbVie, was published in the journal Chem.

Chemical catalyst turns 'trash' to 'treasure'
Chemists find 'huge shortcut' for organic synthesis
Creating global bonds

Tuesday, February 4, 2020

Physics secrets of giant bubbles

A study inspired by street performers making gigantic soap bubbles led to a discovery in fluid mechanics: Mixing different molecular sizes of polymers within a solution increases the ability of a thin film to stretch without breaking. The journal Physical Review Fluids published the results of the study by physicists at Emory University.

The findings could potentially lead to improving processes such as the flow of oils through industrial pipes and the clearance of polluting foams in streams and rivers. The results also hold implications for backyard bubble-blowing enthusiasts.

“This study definitely puts the fun into fundamental science,” says Justin Burton, associate professor of physics at Emory University and senior author of the paper.

Click here to read the full story, including Burton's favorite recipe to make your own giant soap bubbles.

Emory physicist Justin Burton, left, experiments with giant soap bubbles on the Quad with Stephen Frazier, who received his masters in physics from Emory and is first author of the discovery. 

How lifeless particles can become 'life-like' by switching behaviors
The physics of a glacial 'slushy'
Physicists crack another piece of the glass puzzle