x-ray crystallography

A Ph.D. in structural virology

September 8, 2017 By Samantha Kummerer in Research Tags: x-ray crystallography

Gres reflects on the dissertation in HIV research

Anna Gres studies HIV capsid protein using X-ray crystallography. She recently finished her five-year research project at the Bond Life Sciences Center. | photo by Roger Meissen, Bond LSC

By Samantha Kummerer, Bond LSC

Ph.D. candidate Anna Gres frequently described her success at the Bond Life Sciences Center as being lucky.

“It was challenging and stressful, but I think everything worked out well for me and I was lucky in a way. I was fortunate to get to the good labs, interact with great people, attend courses, attend conferences and grow both professionally and personally,” she said.

Her mentors and colleagues use other words to describe her.

Bond LSC scientist and mentor Stefan Sarafianos called her “super spectacular” and her work “nothing short of outstanding” when introducing Gres before her dissertation defense on September 1.

When Gres came to the University of Missouri five years ago as a chemistry student, she knew she wanted to learn about crystallography, a technique that examines the precise arrangement of atoms and the geometry of molecules by looking at the image of the crystal under an X-ray beam. This interest led her to Sarafianos’ lab and into research on HIV.

“I learned a lot of new and exciting things, and I love this about research in general, you have multiple opportunities to evolve if you invest time,” Gres said of her time in Bond LSC. “I’m thrilled I decided to pursue a Ph.D. and do research. It’s definitely something I enjoy a lot.”

She studied a specific HIV protein. Her research involved using X-ray crystallography to determine the structure of the HIV-1 capsid protein. The capsid surrounds the virus’ genetic material, protecting it from a cell’s defenses while transporting the viral DNA to the cell nucleus. Her research produced one of the most complete models of the capsid protein. Previous attempts to understand the protein worked with engineered versions of it rather than the native version.

Gres’ research was the first to reveal the closest representation of the hexameric capsid lattice in intact HIV-1, a discovery that will open the door for further insights.

She explained this knowledge allows scientists to understand the viral life cycle better, study interactions of the viral protein with cellular proteins, further develop capsid-targeting antivirals and improve current ones.

Anna Gres spent her time at the University of Missouri researching the shape of a protein that impacts HIV. She will be leaving HIV research behind when she moves to Sweden for a post doctorate position. | photo by Roger Meissen, Bond LSC

Gres also studied complexes of capsid protein with host cell factors and small molecules that interact with the protein and prevent infection. Other time in the lab was devoted to exploring more than 30 mutations in the protein. Around half of the mutants still need to be completed and analyzed.

Currently, no approved drugs target this protein although it plays a critical role in the virus. Previous clinical trials failed, but recently the protein re-emerged as a promising target. Earlier this year, Gilead, a biopharmaceutical company, announced it would begin capsid inhibitor testing after initial studies revealed its potential as a treatment strategy.

When Gres finished her dissertation defense, she did so with tears in her eyes as she thanked her mentors, family, and friends for their support throughout this five-year journey.

“Work can be stressful; sometimes you need to vent because ‘the project is not working.’ It’s nice when you have people who can listen to you and calm you down and tell you it’s going to work out eventually,” she said.

Her research more than worked out and will continue to provide insights on the disease that affects millions each year.

As for Gres, she is leaving HIV research and the United States behind.

Soon she will be moving to Sweden to start a post doctorate position at the Uppsala University studying chromatin remodeling factors. Gres will bring her skills in structural biology and will transition to cryo-electron microscopy. She explained the topic would be new for her, but that’s why she chose it, so she can continue learning.

Gres receives Von Schwedler Prize

April 5, 2016 By Roger Meissen in Research Tags: Cold Spring Harbor Laboratory, HIV, retrovirus, x-ray crystallography

Work on HIV capsid proteins earns prestigious retrivology award

Anna Gres studies HIV capsid protein using X-ray crystallography. She recently won the 2016 von Schwedler Prize, which awards her $1,200 and gives her the oppportunity to speak this spring at the Cold Spring Harbor Retrovirus Meeting, one of the largest retroviral research conferences in the world. | photo by Roger Meissen, Bond LSC

Science is all about structure in the work of Anna Gres.

For the past four years, she’s looked closely at one HIV protein to figure out its shape in order to stop the virus.

“Capsid protein is extremely important during the HIV life cycle. About 1,500 copies of it come together to form the protective core around the viral genome,” said Gres, a graduate student in the lab of Bond Life Sciences Center’s Stefan Sarafianos and a Mizzou Ph.D. candidate in chemistry. “So, if you are able to somehow disrupt the interactions between the proteins or make them different, the virus loses its infectivity.”

Gres takes her work on this protein to a national stage next month when she speaks at the Retroviruses meeting at Cold Spring Harbor Laboratory — one of the most prestigious international conference on retroviruses — as the recipient of the 2016 Uta Von Schwedler prize. The prize recognizes the accomplishments of one distinguished graduate student as they complete their thesis.

HIV capsid protein has been studied for almost 30 years, but it’s been tricky to get a precise depiction of what it looks like. Gres uses X-ray crystallography to essentially capture the protein in all its 3-D glory. This method gives scientists the higher resolution picture to study the molecular structure of capsid protein. Her work allows the Sarafianos lab and others to study how it interacts and connects with other capsid proteins and the host protein factors of the cell HIV is trying to take over.

“In the past scientists had been splitting the capsid protein in two halves and crystallizing them separately. Another approach was to introduce several mutations to make it more stable,” Gres said. “You would think that it shouldn’t really matter if we have a few mutations, but the protein behaves in such a way that even slight changes result in subtly different interactions that are enough for the virus to lose its infectivity. We were able to crystallize the native protein without any mutations and that should give us more accurate picture.”

Now that the Sarafianos lab and Gres have a good idea of what that native protein looks like, they’ve moved on to other mutated versions of the protein that impair virus infectivity. This could give them insight into how scientists can stop HIV.

“Many labs reported numerous mutations in the capsid protein over the past 25 years that either increase or decrease the stability of the core, which often results in a noninfectious virus,” she said. “Right now we are interested in seeing what structural changes accompany these mutations and how they can affect the overall stability of the core.”