With the ability to treat diseases ranging from scarlet fever to meningitis, Penicillin may be the most well known example of a natural product that has been repurposed as a drug.
“Investigating the Relationship Between Sequence and Function in Type II Polyketide Acyl Carrier Proteins,” the chemistry thesis of Marco Rivas ’18, explores the protein assembly lines within microorganisms that synthesize naturally occurring substances, like penicillin, that have medical or pharmaceutical potential.
Rivas’ thesis represents a continuation of the research efforts undertaken by past Haverford students and his advisor, Assistant Professor of Chemistry Lou Charkoudian.
“The project started two years ago in the 2016 biochemistry Superlab,” Rivas said, “Lou was always there to help whenever I had confusing data or I had trouble finding patterns. [Chemistry Research Associate] Bashkim Kokona was also instrumental in helping me conduct my research, as he is the resident expert on the techniques I used.”
For Rivas, a Chesick Scholar who also completed a concentration in biochemistry, his research was not only a major personal accomplishment, but also helped him earn several awards at graduation including the Lyman Beecher Hall Prize in Chemistry, which recognizes outstanding accomplishment in the major coursework and research. At the end of his junior year, Rivas also received the Arnold and Mabel Beckman Foundation Award for outstanding undergraduate students in chemistry and biology, which funded two summers and a school year of research.
“I’m pretty proud of being a first-generation college student,” he said, “and very grateful of all the sacrifices my parents and brothers made to help me get to this point.”
With continued support from the Beckman Foundation, Rivas is spending this summer in Charkoudian’s lab continuing his research efforts on the potential of natural products as medical drugs. This fall, he begins a full-time job in San Francisco at Collective Health, a company that streamlines the healthcare delivery system through technology.
What did you learn working on your thesis?
I learned a lot of important biochemical techniques, such as protein expression and purification. More broadly, I learned a lot about being independent in the lab and having confidence in my ability to carry out novel science research, as well as how to use what has been done in the past to inform current research. I learned a lot about the importance of collaboration and communication as well. The team for this project was pretty big!
Without a doubt I think gaining confidence to speak up and make suggestions is the biggest takeaway. At the start of my college career, I really doubted myself and felt I did not have much to offer the research world, especially as someone with so little exposure to higher education and research (particularly as a low-income, first-generation college student). As I start to wrap up my time here, I feel like I belong and have a lot to contribute to chemistry.
What are the implications for your thesis research?
In terms of the big picture, this is a (baby) step towards the synthesis of novel drugs. …Lots of natural products are repurposed as drugs, and they are made by these assemblies called synthases. These synthases are made up of different enzymes. One really cool thing you can do is make “unnatural” synthases by taking different enzymes from different organisms and pathways and combining them together to make a new hybrid synthase. However, our limited knowledge of the acyl carrier protein seems to be holding this approach back. In this research we identify a few sequence-stability and sequence-function relationships that is a starting point for expanding our knowledge of how the ACP works, and hopefully we can apply this knowledge to the creation of these hybrid synthases.
“What They Learned” is a blog series exploring the thesis work of recent graduates.