UB researchers receive $1.35 million grant to shed light on ‘dark matter of biology’

A UB-led team of researchers has received a $1.35 million grant from the National Institutes of Health (NIH) Common Fund for Glycoscience to increase knowledge of glycans, a common but little understood class of biomolecules that help bacteria attach to host surfaces, including those in the mouth.

The three-year grant will allow the researchers to collect oral bacteria from humans, horses, cows, sheep, rodents and other mammals. The goal is to harness tools that ultimately help scientists examine how the microorganisms bind to glycans in the mouth to form dental biofilms — more commonly known as plaque — increasing the risk for cavities and periodontal disease.

Glycans exist throughout the body within all living organisms and vary between species and by the individual. Yet, due to their incredibly complex structure, little is known about their biological functions and roles in disease.

Bacteria attach to host tissues by building custom appendages called adhesins that enable them to bind to their host’s glycans. However, to prevent being targeted by pathogens, new glycan structures are invented by the host.

The constant changes force bacteria to play catch up by evolving with the host. Researchers, on the other hand, have difficulties keeping up with the study of glycans due to the need for complex analyses that can only be completed in specialized labs outfitted with expensive equipment.  

“My collaborator Ajit Varki calls glycans ‘the dark matter of biology’ because they remain vastly unexplored,” says Stefan Ruhl, principal investigator and professor in the Department of Oral Biology, School of Dental Medicine.

“We know too little about their function in health and disease. They are by orders of magnitude more diverse than the genome and represent the next challenging frontier in the biological sciences.”

The research is one of several projects supported through the NIH Common Fund for Glycoscience, and is the only one that includes dental research. The study is also led by Paul Sullam, co-principal investigator and professor in the Department of Medicine at the University of California, San Francisco.

The project includes additional investigators from UB; University of California, San Francisco; University of California, San Diego; University of California, Davis; University of Maryland; Emory University and Cornell University.

The study will use friendly bacteria harvested from the mouths of humans and animals to mine for serine-rich repeat (SRR) proteins, a well-studied class of bacterial adhesins that are highly variable and able to bind to a wide range of glycans.

Using genetic information, the researchers will artificially reproduce the variable, glycan-binding pockets of SRR proteins. After testing the proteins for their ability to bind to their target glycans, the adhesins will be mass produced to create affordable, easy-to-use toolkits for scientists who are interested in glycan analysis but lack expertise in glycoscience.

“We do not need to invent such tools. Nature has already created them for us. They are ready and out there. All we do here is to harvest them straight from the mouth,” says Ruhl.

Since bacteria evolved to match the glycans in their host environment, the adhesins will offer clues to patterns and characteristics within the millions of potential glycan structures in both biological and pathological samples.

To learn more about the research being completed under the NIH Common Fund for Glycoscience, visit the NIH website.