Built in 1965, Dana Chemistry Hall is one of the older buildings on the Bates College campus. Don’t let the aged exterior deceive you, though: the students and professors working inside Dana are producing cutting edge ideas and scientific creations. One recent exemplar of this pioneering work was the 2017 synthesis of the Bobcat339 molecule. Named for our school mascot and the page of a student researcher’s notebook which detailed its creation, Bobcat339 has potential to control the functions of genes related to cancer and long-term memory.
The molecule was developed in the lab of Andrew Kennedy, Assistant Professor of Chemistry and Biochemistry. In early 2019 the article, “Cytosine-Based TET Enzyme Inhibitors” was published, which provided an outline of the chemical structure of the molecule and its possible implications for treating diseases. In addition to Kennedy, several Bates students, who have since graduated, co-authored the paper: Emma Jarczyk ’17, Joseph Alp ’18, Kelly Wassarman ’18, Haoyu Sun ’19, Nathanael Kuzio ’19, Michael Bennett ’19, and Gabriella Chua ’18 who was the lead author. Martin Kruse, Assistant Professor of Biology and Neuroscience, also contributed to the publication.
Bates College currently has a provisional patent on the molecule which protects the college’s intellectual rights for a year, before hopefully a full patent with a longer life will be granted. The idea that a single molecule could have implications in treating such seemingly illnesses such as cancer and long-term memory disorders is remarkable and simultaneously difficult to wrap one’s mind around. Kennedy will tell you, though, that the idea isn’t so far-fetched. “I think to someone from the outside,” Kennedy explained, “Or looking on it from the first time to see the idea that somehow a single thing or biochemical pathway could be important in things like cancer and memory is weird. But, at a basic biochemical level, they are very much related.”
In order to explain the molecule’s function, it is important to understand a few biochemical processes taking place in the body. Kennedy, whose lab primarily studies memory and how the three-dimensional structure of genes is affected by learning, set up the background for understanding how Bobcat339 works. He explains that the brain is made of molecules and atoms and “that means your thoughts and your emotions, your memories, these things that we think of as abstract, are made manifested by molecules.” In order for your memories to be encoded into long term memory, it is necessary for your genes to be used and organized differently. An important process required for long term memory to occur is a biochemical reaction called DNA methylation.
DNA methylation is a reaction that occurs on DNA. Although it does not change the genetic code or your genome, it does change whether that part of the DNA is readable or not. Kennedy provided a helpful metaphor: “You can think of it as redacting something: the language is still there underneath the redaction but you can’t read it.” He continues, “that needs to happen in certain genes for more memory to be encoded into the long term. If you block it, you block long term memory.”
Working with this principle of DNA methylation, the students in Kennedy’s lab had the idea to design a molecule that could affect DNA methylation, which in turn has an effect on the properties of the cell. To accomplish this, they structured the molecule three dimensionally using computational methods, and then they synthesized them in the lab. “What we are doing now is seeing if Bobcat339 can affect memory in animals,” said Kennedy.
So, to answer the question of how the Bobcat339 molecule can also have implications in treating cancer, you have to think about how all cellular process are affected by the changing structure of the genome, and how the genome is read. As Kennedy put it, “It turns out DNA methylation is really important for cancer cells becoming more malignant, changing the aggressiveness of cancer. Whereas changing how genes are read is necessary for long term memory. Most of the people who have contacted me, other researchers, asking to use the compound have been in the field of oncology, because they are interested in how this thing effects cancer malignancy.”
There is a long process ahead before the molecule could potentially be approved by the FDA. The publication at the beginning of the year established the chemical structure of the molecule, but there is still a large amount of research and testing that needs to take place.
That being said, Kennedy is impressed by the Bates researchers and how quickly the project progressed: “The students who worked on this were absolutely amazing, they were incredible. It is really really unusual to have a project work at any institution this quickly. The idea that it would happen at a small college that has an emphasis on educating the whole person, and on research is really cool. I think it’s also surprising to some people in the research field.”