BUFFALO, N.Y. – The National Institutes of Health has awarded the National Crystallization Center at the University at Buffalo a five-year, $5.5 million award so that it can continue to advance pioneering research in the field of structural biology.

The new grant builds on the center’s initial NIH award from 2021, which established the NCC at the Hauptman Woodward Medical Research Institute, now part of UB and called UB-HWI, as an NIH National Resource, a designation indicating that it provides a critical service to an extensive national user base of researchers at universities, research organizations and industry. It also builds on Buffalo’s history over the past century – including late UB faculty member Herbert Hauptman’s 1985 Nobel Prize in Chemistry – of continuing to play a major role in crystallography and structural science in general.

“The University at Buffalo is a preeminent pioneer in medical research,” says U.S. Senator Chuck Schumer. “I’m excited that UB has earned a whopping $5.5 million in federal funding to continue cutting-edge structural biology research. This investment will ensure UB’s research has continued access to state-of-the-art technology while translating lab research into real-life treatments for patients. I will never stop supporting medical research in New York and across the country.”

“The University at Buffalo is a pioneer in medical research and ingenuity,” says U.S. Senator Kirsten Gillibrand. “I am proud to have fought for the NIH funding behind this grant for their National Crystallization Center, which is paving the way for advancements in structural biology. This support is vital to understanding disease, and I will keep pushing for the resources necessary to continue this life-saving work.”

“This investment is a vote of confidence in Buffalo’s role as a national leader in biomedical research,” says Congressman Tim Kennedy (NY-26). “The National Crystallization Center is giving researchers across the country the tools and expertise they need to understand the molecular structures behind disease and identify new pathways to better treatment. From infectious disease to cancer and addiction, this work happening in Buffalo has the potential to shape how we understand and treat the most pressing health challenges facing the world today. I’m proud to see this critical research continue to grow here in Buffalo, and I’m grateful to the scientists at UB-HWI who are putting our community at the center of discoveries that can benefit people across the country and around the world.”

Since 2021, the NCC has worked with approximately 475 users from 238 different academic research groups from 133 different institutions. NCC users are from 34 states, Puerto Rico, the District of Columbia, and four countries.

“The National Crystallization Center gives researchers across the country access to high-throughput crystallization and advanced imaging capabilities unavailable at most academic institutions,” explains Marc Halterman, MD, PhD, senior associate dean and executive director of the Office of Research in the Jacobs School of Medicine and Biomedical Sciences at UB. “These technologies accelerate structural discovery, providing new insights into disease and opportunities for therapeutic development. Having this resource at UB-HWI builds on Buffalo’s legacy in structural biology while positioning UB at the forefront of structural science and biomedical discovery.” 

Over the past five years, a few of the many notable advances accomplished by the NCC include determining the structures of a possible treatment for nicotine addiction, inhibitors of the SARS-CoV2 virus, and possible inhibitors of a protein involved in making metastatic cancers drug-resistant.

The new grant will allow the NCC to maintain access to state-of-the-art instrumentation and unique high-throughput capabilities, expand optimization efforts to maximize crystal production, provide crystallization expertise and training and develop new computational tools and resources. It will also allow UB-HWI investigators to host visiting scientists and fund more workshops for users, which have become so popular that they are often overbooked. 

Sarah E. J. Bowman, PhD, associate professor of biochemistry in the Jacobs School, is director of the NCC and principal investigator on the grant; she was also PI on the original grant. Other key personnel include co-investigator Miranda L. Lynch, PhD, research assistant professor in the Department of Structural Biology in the Jacobs School, and Gabrielle R. Budziszewski, PhD, operations manager of the NCC at UB-HWI.

Bowman explains how crucial structure determination is to advancing the study of disease and the development of new drugs.

“Our goal with structural biology is to hypothesize about the function of a protein given its structure,” she says. “How can we design a drug to change the function of disease-causing mutations in proteins? It all depends on having a really detailed idea of the protein’s structure.”

That requires first crystallizing the protein, optimizing the crystals that are produced, and then sending the sample to a synchrotron where the crystal is bombarded with high-powered X rays that create a diffraction pattern. Computational methods then translate that pattern into a three-dimensional structure.

Bowman and her colleagues wrote the new NCC grant application to enhance the support they provide to users at multiple points in the process.

“At the NCC, we are really focused on helping users with finding the best conditions to grow their crystals and then to help them with optimization,” she explains. “It turns out that finding which conditions will actually generate a crystal from your sample is one of the major bottlenecks in the process.”

The NCC is well-equipped to tackle that bottleneck because of its unique high-throughput crystallization screen. It was developed in the early 2000s with funding from the Protein Structure Initiative by researchers at HWI. 

“We are the only center in the world that has this screen, which allows us to screen through 1,536 different conditions on one plate that’s about the size of a cellphone,” Bowman says. “It’s been the workhorse of this center. It’s like each of the 1,536 wells on the plate is its own experiment.”

Bowman emphasizes the iterative nature of what NCC does. Once users send a sample to the NCC, there is significant collaboration as team members provide assistance to users on how to get the best crystal from a particular sample. The new funding enables expansion of NCC assistance to users in optimizing the conditions that produce the best crystals.

“We help find the best conditions for crystallization, optimize those conditions and harvest the crystals,” she says.

The crystals that are produced through the high-throughput process are scored by the NCC’s AI-based tool called MARCO (MAchine Recognition of Crystallization Outcomes). After the optimization process, the crystals are ready to be sent to one of the nation’s five synchrotrons, which are also NIH funded. With the new grant, the NCC will continue to provide assistance to users as their samples undergo diffraction at the synchrotron.

“Our user base continues to grow,” says Bowman. “With the new grant we will continue to educate people and to continue to spread this knowledge. It feels amazing.