The Caudy research group has made strides in understanding how the building blocks of our genetic code are made. Specifically interested in the metabolism of cells, the Caudy group has also studied the connection between cancer cells and metabolism.Dr. Amy Caudy is currently a professor in the Department of Molecular Genetics and also serves as the Canada Research Chair in Metabolics for Functional Enzyme Discovery. She was previously a fellow in the Lewis-Sigler Institute for Integrative Genomics at Princeton University.The Varsity spoke to Caudy to discuss her group’s work and how the breakthroughs being made now in the field of molecular genetics will affect both research and cancer treatments in the near future.The Varsity: What is molecular genetics?
Amy Caudy: I think of molecular genetics as an approach. We have the sequence information — which we can now get easier than ever before — and we have all the tools to analyze it. We now even have the tools to go in and change that sequence. You can go and figure out what the genes are from your [DNA] sequence analysis and experiments, and you can make hypotheses. The molecular genetics comes in because you’re changing the molecule itself; you’ve got the DNA molecule and genetics to create organisms that test your hypotheses. Genetics is trying to understand what the instructions in the DNA are and how the DNA is read to ultimately produce an organism. We have a three billion base pair set of DNA in our genome, and [because of DNA] here we are talking to one another. That three billion base pair set is only 20,000 genes. What are those genes and how are they interacting? Genetics as an approach is similar to this analogy: If I pull a piece out of my car, will the car run or not? In a sense, what’s the resulting phenotype? If I make changes to the instructions of the cell, what’s the result at the end?TV: What is cellular metabolism?AC: It’s how the nutrients we take in — for us that’s food, for yeast that may be the barley broth that you put them in to make beer — how those nutrients are broken down and converted into the building blocks of the cell. It’s a set of chemical reactions. There are thousands of reactions, and there’s enough flexibility there that we can eat a variety of things and make exactly what we need to sustain growth.TV: What don’t we currently know about cellular metabolism?AC: We have hundreds of compounds in cells and we don’t know what they are or how they’re being made. Typically, they’re being made by an enzyme reaction. We’ve got things in cells that are being made by a gene but we don’t know the gene, and we also have reactions that we know are occurring that have to be catalyzed by a gene. We also don’t know many of those genes. We also often don’t know the direction of chemical reactions in cells. We have ideas from studying things like cows’ hearts, but we’ve made a lot of generalizations from organs that are easy to study but don’t necessarily represent what’s happening in the majority of cells.TV: What does the Caudy group hope to uncover by researching cellular metabolism?AC: The best drugs we have are small molecules that inhibit enzyme reactions. However, we don’t know all [of the cell’s] enzyme reactions. My lab’s trying to figure out what those reactions are, and the end goal is to inhibit cellular growth of bacterial pathogens or cancer cells by targeting unique metabolic aspects of cells.TV: Some of the research in your lab focuses on cancer. How does cancer link to cellular metabolism?AC: Cancer takes up glucose at a much higher rate than normal cells. That’s one example of how the metabolism of cancer cells [is] different. Also, they’re actively growing. Classic therapeutics take advantage of this by targeting DNA synthesis [to kill cancer cells]. Only cancer cells, and a few cells like those in your gut and your hair, are actively growing. The rest of you doesn’t really need to do much DNA synthesis, so you’re actually fine to kill the cancer by inhibiting DNA synthesis. This is better than any other option that we have right now. My hope, in my lab, is to find pathways that are even more cancer-specific than DNA synthesis, and are involved in how cancer upregulates its metabolism to grow effectively.TV: Your work helped to discover a new pathway for the synthesis of ribose in the cell. What is ribose, and how has this finding been significant so far?AC: Ribose is the sugar that is in RNA, the messenger molecule, and deoxyribose is the sugar in DNA. Deoxyribose is made directly from ribose, so you have to make ribose to transcribe and replicate your genome. This pathway we found is specific to fungi and also is present in a small group of bacteria — we’re very interested in that apparent transfer of genetic information from bacteria to fungi, and that’s an active area of research. This is also very important for biofuels, because metabolism of ribose and other 5-carbon sugars is important for knowing how to break down plant sugars.TV: The field of molecular genetics is moving at a rapid pace — what questions do you feel molecular genetics and metabolism research will be asking in the next 10 years?AC: I think that molecular genetics is going to be transformed by the availability of [DNA] sequence information. We’re at this point where lots of people are getting their genomes sequenced. Now, cancer patients at many cancer centres are routinely having their tumours sequenced. When you do this, we get a ton of information. We need to be able to use this data to say, “How can we create a therapy relevant to you?” The real goal is that someday, healthy people will look at their genomes and notice their risk factors for certain diseases. From this, they’ll hopefully say, “What can I do today so that I remain healthy years from now?”This interview has been edited and condensed for clarity and length.