Research on the HIV-1 Integrase Protein

Nathan Stewart, COL ’24, Royal Oak, MI

This summer, I had the opportunity to work in the Gupta/Van Duyne lab at Penn Medicine’s department of Biochemistry and Biophysics, performing research related to the HIV-1 integrase protein. I went in without knowing many of the full procedures to studying proteins, such as the processes of expression and purification. Luckily, the ability of working full time during the summer in the lab has given me great insight into how research is performed in academia, and more specifically in my intended major as well. I also got to collaborate with other faculty, give presentations, assist high-school students, and even travel to Brookhaven National Laboratory in New York to carry out SEC-SAXS and X-Ray crystallography experiments.

This experience helped develop my skills in performing research and being able to carry out experiments from start to finish by myself. The work I carried out built and strengthened my independence in all aspects that a research position requires, like planning and carrying out appropriate experiments, addressing concerns and learning how to overcome setbacks, properly analyzing data, and presenting my findings to others. The independent nature of this opportunity also allowed me to understand my weaknesses and figure out what I can improve on as I continue my time in academic research. Working in a biochemistry/biophysics lab also strengthened my biochemical knowledge with techniques such as size exclusion and nickel chromatography and SDS-PAGE. I also can now independently grow bacteria to express my desired protein, and from there isolate and purify my desired protein from the numerous other proteins present. This purified protein is then what can go into analytical experiments.

For me, working with the HIV-1 integrase protein has been extremely fascinating, where I got an in-depth experience into the 3 different domains of the protein, with a larger focus on the catalytic core domain (CCD) and the carbon terminal domain (CTD). The CCD has been a large focus for pharmaceutical companies since numerous drugs can act as an allosteric inhibitor of integrase (ALLINI), which will prevent viral maturation of the virus in the host. This is so that infected people can keep a low viral load and lower the possibility of spreading the virus. Similarly, it has been wondered if it is possible to inhibit HIV-1 integrase via its CTD, since it seems to play another important role in viral morphogenesis. Thus, if an inhibitor or disruption is designed to affect the CTD, it could become an alternative treatment method to the already known ALLINIs that interact at the CCD. This is why structural data and information about protein binding, which are obtained in research laboratories, are necessary for further research and pharmaceutical design to effectively design a drug to possibly address this step in HIV maturation.

Research to gain more information about the structure, function, and biochemical interactions of the HIV-1 integrase protein is what is helping move the methods of HIV treatment in the right direction. Overall, not only was I able to learn many essential biochemical and biophysical lab techniques, but I also got to learn more about how research connects directly to the goal of patient treatment.

This is part of a series of posts by recipients of the 2022 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.

By Career Services
Career Services