Building molecules, studying symbioses between species, and exploring how life evolved

At the Carl R. Woese Institute for Genomic Biology, scientific questioning occurs across a wide scale—including the creation of the smallest molecules, interactions between plants and animals, and the exploration of life on distant planets. This kind of interdisciplinary research is necessary when conducting cutting-edge science and asking highly integrative questions about how life functions. The major institutes at the IGB both past and present have been involved in conducting research along this massive scale are the Molecule Maker Lab Institute, the Genomics and Eco-evolution of Multi-scale Symbioses, and the Institute for Universal Biology.  

Molecule Maker Lab Institute
The advent and accessibility of the 3D printer helped with advancements in so many fields of science: medicine, engineering, and research. It offered flexibility and cost reduction of components that scientists wanted to create, as well as being quicker and easier to design. Similarly, 3D printed molecules could enable the discovery, understanding, and synthesis of molecules in a host of different research fields. This was the goal for establishing MMLI in 2020, after receiving a 5-year, $20 million grant from the National Science Foundation. The project is led by MMLI principal investigator Humin Zhao (BSD/GSE leader/CABBI/CGD/MMG), Steven L. Miller Chair and professor of chemical and biomolecular engineering, and Kenton McHenry, the National Center for Supercomputing Applications’ Associate Director for Software.

“Over the past decade there have been major advances in both AI and automated chemical and biochemical synthesis, making the timing for the launch of the MMLI both judicious and urgent,” said Zhao. “Synergistically integrating these powerful disciplines now has the potential to dramatically accelerate and advance the manufacturing and discovery of molecules with important functions that address major unsolved problems in society. Not doing so would result in a major missed opportunity for the U.S. research community,” Zhao said.

MMLI combines advanced artificial intelligence with machine learning methods to design and synthesize small molecules, peptides, and oligonucleotides, as well as characterize the reactions and properties of those molecules. Using this technology, MMLI seeks to streamline molecule manufacturing and discovery, making it more accessible and efficient for scientists.

The MMLI team involves researchers from across the University of Illinois, including the Grainger College of Engineering, the College of Liberal Arts and Sciences, the Beckman Institute for Advanced Science and Technology, and the NCSA, as well from the University Laboratory High School, Northwestern University, Penn State University, and Rochester Institute of Technology.

The projects at MMLI are highly diverse and integrative, including linking genetic sequence to function across suites of proteins, creating a finely-grained database of COVID-19 biomedical discoveries, and harvesting photovoltaics to make more efficient solar panels. The institute is also involved in outreach, creating both a physical and digital molecule maker kit that children in classrooms can use to build and learn about specific molecules.

Genomics and Eco-evolution of Multi-scale Symbioses
Everything in the world, animals, plants, and even humans, are entrenched in microbes. Microbes can have dramatic impacts on the behaviors, functions, and genomics of their host organisms, and these can extend to effects beyond the microbe-host system, to larger scale ecosystems. Furthermore, these interactions can be both beneficial and detrimental. It is clear that understanding these interactions, or symbioses, is important in order to influence their impacts on individuals and ecosystems. However, such an endeavor requires a highly integrative team to explore nested interactions across multiple disciplines.

GEMS was created to address this question after receiving a 5-year, $12.5 million grant from NSF in 2020. The team is highly disciplinary, consisting of 27 professors from microbiology, plant biology, entomology, ecology, evolution, computational biology, and education, and is led by microbiology professor Rachel Whitaker (IGOH leader/BCXT), evolution, ecology and behavior professor Carla Cáceres (IGOH), and plant biology professor Katy Heath (IGOH) from University of Illinois, ecology and evolution professor Mercedes Pascual from University of Chicago, and biology professor Irene Newton from Indiana University.

“The inspiration behind GEMS is to integrate biology since all too often, fields of biology are siloed by funding, approach, language and culture. Surprisingly, some of the most significant divides on many campuses are between molecular and organismal approaches to biology. Because microbes lie at the interface between these spheres, our focus is on bringing the natural microbial world into view to integrate biology,” said Whitaker.

Using the symbiosis between flowering plants and pollinators as a model system, the institute explores how phenotypic variation via nested symbionts affects species’ traits, and stability of interactions across different species levels:  plant–pollinator, legume–rhizobium, honey bee–microbiome. With the changing climate and emergence of new diseases affecting both plants and pollinators, it is important to understand how microbial interactions at the genetic and molecular level can play out to larger scale ecological effects on the pollinator system.

The Institute for Universal Biology
In the mid 1900s, the tree of life was thought to have two branches – bacteria and eukaryotes. Carl Woese rewrote the tree of life after discovering that Archaea are genetically distinct from bacteria, creating a third branch on the tree. All current life once descended from a common ancestor 3.5 billion years ago, begging questions of what this early ancestor was like, and what was needed for such life to evolve. Furthermore, could delving into early evolutionary states of life on earth help scientists discover potential for life on other planets?  
IUB was established in 2012 to address this very question – is there life beyond earth? The institute was created after receiving from the National Aeronautics and Space Administration a 5-year, $8 million grant, which microbiology professor and IGB namesake Carl Woese was involved in, awarded shortly before his passing.

“Modern genomics provide the data and tools to examine carefully the evolutionary relationships between parts of the cell.  And even further, theory gives us a clear hypothesis to test: namely that early life was a commune, and indeed had to have been, based on general universal biology considerations related to the detailed structure of the genetic code,” said Nigel Goldenfeld, former Leader of the Biocomplexity Research Theme.

The team combined theoretical work, used to look back into evolutionary time and understand the early collective states of life, with microbial and genomic experiments to study how cells sense, respond, and adapt to their ever-changing environments. IUB also explored major transitions that life underwent from being communal to having separate organismal lineages. By studying the evolution of life on our own planet and understanding the properties needed to facilitate it, researchers can make inferences about whether any distant planets could also be vectors for life.

“It is important to develop the field of universal biology, because we may never find traces of life on other planets.  But if we understand that life is generic, maybe even an expected outcome of the laws of physics, then we’ll know for sure that we are not alone,” Goldenfeld said.