A crystal clear path to discovery

The colorful Ray of Hope sculpture at the entrance of The Hormel Institute, University of Minnesota, is a symbol of a major achievement in the institute’s long list of historical successes, as well as its unwavering commitment to scientific progress.

The 30-foot sculpture, installed in 2016, depicts the structure of ribosomal S6 kinase, a protein studied by researchers at the institute who discovered its role in melanoma, and its binding with silybin found in milk thistle, which functions as a natural anticancer agent. Their discovery of this link was a game changer in fighting melanoma, and a $4.3 million investment in a cryogenic electron microscope that same year could pave the way for further advancement in the field of cancer research drug design.

Cryo-electron microscopy (Cryo-EM) is one of the most powerful structural biology techniques currently available, allowing researchers to rapidly uncover the structure of proteins and other molecules at near-atomic resolution.

The cryo-EM facility was part of a wider $27-million expansion that also saw the recruitment of several structural biologists, such as Dr. Amer Alam. Attracted to The Hormel Institute’s excellent structural biology facilities, and its strong cell biology and translation research focus, Alam joined The Hormel Institute faculty this year.

“Visualizing structure can help us understand cellular physiology at the molecular level, aid in understanding disease progression and help develop drugs and novel therapeutic strategies for various diseases,” says Alam.

He studies the structural biology of membrane transport processes and, during his postdoctoral training, used cryo-EM to elucidate the first structure of human p-glycoprotein, a multidrug effux pump, in a lipid environment and in complex with the commonly used chemotherapeutic drug Taxol.

Alam explains that the protein detoxifies cells, but can also be exploited by cancer cells to gain resistance to chemotherapeutic drugs. Information obtained from its cryo-EM analysis helped understand some of the most fundamental aspects of its physiological functioning that had eluded the field for decades.

Cryo-EM also lured Bin Liu to join The Hormel Institute as an assistant professor this year. Liu’s research focuses on the mechanisms of transcription and how it is regulated, to eventually provide the structural basis for designing effective antibiotics. Before joining The Hormel Institute, Liu spent almost ten years solving structures using X-ray crystallography, a difficult approach that requires large quantities of crystals. In contrast, Cryo-EM can be done with small amounts of samples and without crystals. “[It] makes everything so easy,” says Liu.

The cryo-EM facility features a Titan Krios G2 cryo-electron microscope, a fiber network for fast data processing, GPU (Graphic Processing Units) workstations, and a 2 petabyte mass storage system. Anna Sundborger-Lunna, an assistant professor at The Hormel Institute who studies the mechanisms of cell death, helped design the facility. By participating in discussions about which equipment to buy and how to construct a space based on the needs of the institute, Sundborger-Lunna gained insight into research avenues she had never experienced before.

These resources provide early-career investigators with opportunities uncommon at smaller institutes, where they would typically have to travel to national centers to access such technology. “It’s a pretty big deal for junior faculty to have access to such amazing equipment,” says Sundborger Lunna. “Having this facility here, having this microscope here, has made my research possible.”

On a broader scale, “the cryo-EM facility became a hallmark of how dedicated they are here at The Hormel Institute,” says Sundborger-Lunna. The Hormel Institute will continue its investment in structural biology through the recruitment of new investigators and acquisition of additional technologies for the cryo-EM facility.