April 10, 2023

Team Action for Scientific Solutions: Structural Biology Forum

Written by

Jamil Saad, Ph.D.Jamil Saad, Ph.D.In science, collaboration is about sharing information, resources, and ideas. Collaboration allows faculty to combine their knowledge and resources to form new ideas that might not have been possible by working alone, which leads to better results for everyone involved.

Several groups across the Heersink School of Medicine come together regularly to promote team science in their respective areas of expertise. The Office of Research for the Heersink School of Medicine will highlight the work of these groups in its Team Action for Scientific Solutions (TASS) series.

In this inaugural article, Jamil Saad, Ph.D., professor in the Department of Microbiology, introduces the Structural Biology Forum.

“Structural biology is not new to UAB,” said Saad. “Structural biology research at UAB goes back to 1968, when Charlie Bugg, Bill Cook, and Larry DeLucas used x-ray crystallography to determine structures of nucleic acid components and calcium complexes.”

In 1971, the O’Neal Comprehensive Cancer Center (OCCC) established a structural biology core to support research in areas related to cancer. OCCC support for structural biology cores continues to this day. In 2012, the Center of Structural Biology was established as a University-Wide Interdisciplinary Research Center. Since 2017, structural biology research at UAB has been operating under the umbrella of “Program in Structural Biology.”

“UAB houses over 16 active structural biology labs spread over multiple departments, which makes it one of the largest institutional structural biology groups in the southeast,” said Saad. “To build team science, there is a need for synergy and networking with non-structural biologists. In the summer of 2022, I came up with the idea to establish a Structural Biology Forum (SBF) as a venue for Structural Biologists and non-Structural Biologists to meet and discuss projects of mutual interest. The inaugural meeting of the SBF was held in September 2022.”

The Heersink School of Medicine communications staff sat with Dr. Jamil Saad to gain insight into this program.

Q: What is Structural Biology?

Structural biology is the study of how macromolecules are built and arranged in three-dimensional space to understand how they interact and function. Visualizing how macromolecules are structured at the atomic level helps with understanding how thousands of different molecules in our cells work together to keep us healthy. Structural studies can tell how genetic changes in macromolecules, such as mutations, affect the structure and, therefore, function. Knowledge of the three-dimensional structure of proteins also accelerates drug discovery and development. Determining the three-dimensional structure of a biomolecule is achieved by using a variety of techniques, including cryo-electron microscopy, x-ray crystallography, nuclear magnetic resonance (NMR), and to a certain extent, mass spectrometry.

Q: How did you become involved in this area?

One of my primary interests is to understand the molecular basis for diseases. Our body is a machine that is made of trillions of molecules. These molecules function in an extremely balanced and harmonized manner. Diseases are caused because something goes wrong with how these molecules are built or how they interact with each other.

When I was a graduate student at Emory University, I was interested in understanding at the atomic level how cisplatin, a leading anticancer drug, disrupts DNA replication. I used NMR methods to determine the three-dimensional structure of a DNA duplex bound to cisplatin. To further gain experience in structural biology techniques and their application in disease-related projects, I joined the laboratory of Michael Summers, a Howard Hughes Medical Institute Investigator at UMBC as a postdoctoral fellow.

My postdoctoral project was focused on understanding the mechanism by which HIV-1, the virus that causes AIDS, assembles on the plasma membrane of the host cell to generate new virions. By using NMR, I found that a major structural protein in HIV called Gag recognizes a specific lipid localized only on the inner leaflet of the plasma membrane to initiate virus assembly. It was only possible to understand this specificity when we determined the three-dimensional structure of the protein bound to the lipid.

Q: What activities are offered in this program?

The SBF meets in person once a month. Approximately 50-60 students, postdocs, staff, and faculty attend the meeting every month. Typically, we invite two speakers, a Structural Biologist who presents unpublished data, a technique, or an innovative assay or approach, and a non-structural biologist seeking feedback and collaboration with structural biologists. We also invite an external speaker who applies structural biology techniques to elucidate biological mechanisms of interest to our community. The SBF offers a platform for researchers to meet and discuss research topics and methodologies, share and develop ideas, learn from each other, and gain knowledge. It is also an opportunity for young researchers to showcase their work and interact with senior Investigators.

Q: What is innovative about this program?

The SBF brings together specialists and non-specialists in structural biology to promote collaborative structure-function research in diverse disciplines, including infectious diseases, cancer, immunology, cell biology, drug discovery and design, cell biology, and microbiome/metabolomics. What is unique about it is that it builds bridges between scientists regardless of their expertise, location, affiliation, or scientific interest.

Q: What opportunities are available to faculty looking to participate in or partner with the program?

We are continuously looking for opportunities to build collaborations across campus. We also included Southern Research (SR) in this initiative to foster collaborations in drug discovery and development. With the establishment of the new Biotech Center by SR, there could be new opportunities to build and promote structure-based drug development initiatives with SR. Faculty, students, and postdocs from all scientific backgrounds are welcome to attend our monthly SBF meeting to learn and interact with our structural biology community.

If you lead or are part of a team science group and would like the Heersink School of Medicine to highlight your group’s activities, please email SOMresearch@uab.edu.