Natural, industrial, and agricultural ecosystems all make an impact on human health and vice versa. Studying these impacts is the focus of the Infection Genomics for One Health (IGOH) theme at the Carl R. Woese Institute for Genomic Biology (IGB). This theme comprises researchers from across disciplines, and is led by Dr. Rachel J. Whitaker, professor of microbiology.

“We’re all connected. That is an undeniable truth,” said Whitaker.

“Between the realms of agriculture, nature, and humans, the unifying factor is the microbes that exist in each and the specific genes those microbes carry. The IGOH theme at the IGB allows research to be contextualized, and to exist in a space where lab work becomes immediately relevant and applicable to the rest of the world,” she said.

IGOH: From an Idea to a Theme

The idea for this theme started with three professors: Dr. Rachel Whitaker, Dr. Rebecca Stumpf, and Dr. Carla Cáceres. Each of these three scientists were from different departments, and they shared a desire to understand organismal interactions throughout the course of natural history. Dr. Whitaker saw the theme through its application to the IGB, to its trial phase, to expanding across the nine departments it encompasses today. There are currently ten professors who conduct research within this theme, and only two of them are from the same department.

“We started this theme because we wanted to create a type of hub for information to flow through, to allow people from different departments to work on infection genomics together,” Dr. Whitaker explained.

Prior to the creation of this theme, researchers across the University of Illinois were working on a variety of infection studies, mostly within their own discipline.

Whitaker and others knew that the research would become stronger if they could work together.

“Studying them as a whole makes more sense,” said Whitaker. “For instance, an infectious microbe may travel from a water system into humans, or from the soil, into plants, into livestock. The combinations of transmission go on, and in order to study these pathways, we needed this informational hub for cross-departmental collaboration.”

“Luckily the IGB director, Gene Robinson, thought it was a great idea from the very beginning, and provided us with a space to meet in and lots of encouragement as we got the theme started,” Whitaker said.

This theme was unique compared to anything else the IGB had seen before because it brought evolutionary biology to a modern light, and it allowed infection biology to be examined in a novel way: the studies would be more about the dynamics of infection and how these dynamics impacted evolutionary trajectories.

It’s also established a system of communication between people working in different departments, just as Whitaker had hoped from the start. Between microbiology studies of estrogen levels in humans, to civil engineering projects about drinking water treatment, to anthropology investigations of ancient human interactions, this theme houses a wide variety of projects and disciplines.

For instance, the work Dr. Whitaker is currently pursuing under this theme focuses on multi-level infection genomics in patients with cystic fibrosis. In these patients, Pseudomonas bacteria, a genus that includes several well known species such as P. aeruginosa, P. syringae, and P. putida, can establish a chronic infection in patients, and these bacteria are subsequently infected by bacteriophages. Bacteriophages are viruses that specifically infect bacteria, as opposed to other hosts such as plants or humans. These bacteriophages would normally enter a human body and have no effect on the overall health of the individual. However, in the presence of the bacteria these viruses have an affinity for, they infect the Pseudomonas which have already infected the lungs of a human.

These infection patterns and mechanisms then impact the way the bacteria affect the human who’s serving as their host. Specifically, viral infections of Pseudomonas in cystic fibrosis patients can alter the bacteria’s production of virulence factors. These factors are what make the disease more or less severe in humans, and include any molecules that make the bacteria biofilms that Pseudomonas form more structurally or functionally sound. Depending on the way that mobile genetic elements are transferred between the bacteria and virus during the viral infection, the severity of the disease in the human host can fluctuate.

“This project focuses on the within-host dynamics of infections,” said Dr. Whitaker. “The bacteria are the hosts to the viruses, and their interaction is happening within the human ecosystem.The human microbiome is like a mobile landscape within which the evolution of this chronic infection is taking place.”

These studies will allow scientists to better understand how the environment of a human host will impact the internal evolution of Pseudomonas bacteria themselves. Whitaker says that the results of this work to have been quite interesting, especially after antibiotic treatment of this infection. While the research that has been done is preliminary so far, it suggests that antibiotic exposure in general may trigger evolutionary mechanisms in Pseudomonas.

“It seems as though all the bacteria emerge from one colonization event, which makes them genetically similar. But after antibiotic treatment, they start to evolve within the patients’ lung over time, and we can track that evolution through deep population analysis,” said Whitaker.

By sequencing several hundred samples from different time points throughout an infection, the lab will be able to discern if population variation is predictable, and ultimately that will become a model to predict intra-host dynamics. This will become a piece in the broad and predictive framework that the IGOH theme seeks to develop.

Infection as a Means of Interaction

The word infection tends to be interpreted to mean illness or sickness, but this is not always the case. Infection genomics can include commensal relationships as well as parasitic relationships. Any interaction between two or more organisms can be considered a form of infection genomics, since most interactions involve not only organisms themselves, but their microbiomes as well.

“As humans interact with plants, animals, and the environment, we exchange microbes with one another,” said Whitaker. “These microbes can interact amongst themselves through their mobile genetic elements, small pieces of DNA that allow microbes to communicate and exchange information about survival tactics depending on environmental conditions."

Microbial communication depends on the microbes that are interacting, the genetic elements they each possess, and the environment in which the interaction is taking place. This high number of variables leads to a huge variety in microbial interactions, and is the way those interactions make an impact on their hosts.

However, among these variables, patterns emerge where interactions become similar.

“As these patterns begin emerging across systems studied in different departments, it’s possible to overlay these patterns with mathematical models, which will allow these findings to develop into a broad and predictive framework, which scientists can base future evolutionary theories off of,” said Whitaker. “Building this framework has been one of the main goals of this theme since the beginning.”

“We’re trying to describe an evolutionary framework within real life systems based on evolution and transmission.We’re working towards creating predictive models that fit within the physical structure of what people are seeing in the lab,” Dr. Whitaker explained.

The IGOH theme encompasses this micro-lab work all the way to work done on a macro-scale, such as work currently being done by theme affiliate Dr. Rebecca Stumpf in the Department of Anthropology at the University of Illinois. The Stumpf group has been doing studies examining primate population interactions in Uganda since 2007, and they are presently examining how these interactions affect each population’s internal microbiomes.

“Our more recent studies are focused on examining microbial presence, prevalence and inter-species dynamics among primates, livestock and the environment to identify and hopefully limit pathways for pathogen and antibiotic resistance transmission,” Stumpf said.

“The work Dr. Stumpf’s group is doing is important because this is on- the-ground-type work. It teaches you about real-life connections, and these connections are so important. Knowing how these species interact, when do they interact, and where do they interact, it all makes a difference in the way you would study those dynamics,” Whitaker explained. “You won’t know all that sitting and reading about it in the lab, this work involves going out and seeing the world so your work can replicate the reality that you’re studying.”

Dr. Stumpf’s newest project has recently been funded by the National Institutes of Health (NIH), and will employ metagenomics experts as well as veterinarians, computational biologists, and microbiologists to discover how microbial interactions affect primate health and evolution. This work will be able to help scientists understand what the key factors are in microbiome diversity within interacting populations, whether it’s diet, physiology, mating patterns, or habitat. Again, this work will add to the predictive model that IGOH strives to create surrounding evolution and transmission. 

One Health as a Concept

One Health is an initiative at many institutions with the goal of bringing together the health of all living things under one roof. In this case, One Health represents a concept. “It’s the realization that we are all connected in a way that makes the study of health stronger if we examine the health of the natural world as a whole, rather than in component parts,” she said.

“There have been institutional barriers that have kept groups of people from working together in the past, and One Health is an initiative to allow all of these people to study our connectedness together.”

Whitaker says that it is challenging to study antibiotic resistance in human systems alone, without the context of the rest of the living world. The same type of resistance may have developed in plants or animals, and the resistance found in humans strains may have originated in one of these other areas and been transferred. As long as humans interact with the rest of the world, our health depends on the health of everything else around us.

IGOH and the World

Whitaker: “This theme works helps move lab work from in vitro to in vivo.”

“Rather than learning about life through microscopes or agar plates or line graphs, it’s learning about life in the context of the whole world throughout all of time,” said Whitaker. “One Health is the idea that you cannot study life without knowing where the life you study comes from naturally.”

Of course in order to study infection at the microscopic level, which is where many of the studies within this theme find their roots, it takes a lot of skill in microbiology to attain and interpret data that lead to the findings.

“MCB’s microbiology department has helped us, since the thing that connects us is our microbes.The basic mechanistic understanding comes from microbiology principles. The biology is a piece that you need to build the larger framework we’re trying to build up.We couldn’t do this without the supporters we have in the microbiology department,” Dr.Whitaker said.

The current work that is being done under this theme has endless possibilities for the future of evolution and transmission, finding common ground in research that will allow us to understand life more fully. By allowing infection genomics to encompass all the realms of life, it is possible to create a more broad understanding of humans’ place on the planet.