Jen Gallagher, Geneticist

What is your favorite part about being a scientist and how did you get interested in science in general?

Me at my happy place. On the afternoon before a long weekend, I finally have time to come into the lab and dissect yeast.

My favorite part about being a scientist is going into the lab, doing an experiment, and discovering something that nobody else knows. My uncle was in grad school when I was a kid. He studied fracture mechanics in metals, or crackology, as I like to call it. I visited his lab and he showed me his million-dollar microscope. He was getting a Ph.D. so I decided I would, too. I wasn’t interested in engineering. I liked watching nature shows on PBS and biology in school. In high school, I learned about DNA replication. DNA has directionality and can only be replicated in one direction but there are two strands held together in the opposite direction. When you separate the DNA there isn’t enough space to copy the other strand. The cell solves this problem by making short sections of DNA of the strand that is facing the opposite direction and then gluing them together. These are called Okazaki fragments and I thought that was cool. Also, in that class, my teacher showed us statistics on how many people get undergraduate, masters, and Ph.D. degrees and all the different careers you could do with those degrees. So at 16, I decided to get a Ph.D. and do research in biochemistry. I searched for schools that had strong undergraduate research in a real biochemistry program. I didn’t want chemistry and biology class, but a dedicated program. Once I did start a biochemistry project, I decided that wasn’t for me. Biochemistry involves reducing reactions to their bare minimums, but life isn’t like that. So, I traded the cold room and purified proteins for genetics. I like asking the questions and having the cells tell me the answers.

In laymen’s terms, what do you do?

I investigate why genetically diverse individuals respond differently to the same stress, usually a chemical. Every chemical is a poison in the right dose but also can be a medicine. Water is essential for life is also toxic in high doses. Drowning is a leading cause of premature death. The stress response is a complex reaction. The first thing that happens is that cell growth is arrested. It’s like if your house is on fire. Once you see the fire, you don’t finish washing the dishes and then find the fire extinguisher. There are common responses to stress and then there are specific ones. To find out how the cell’s response to a specific stress, we exploit genetic variation within a species. I compare cells that can successfully deal with the stress to ones that can’t and determine what are the underlying differences that govern that. Depending on the stress we sequence genomes, measure the changes in gene expression or proteins. We work on yeast because in general people don’t appreciate being poisoned and don’t reproduce as fast as in the lab. Yeast have a generation every 90 minutes. Yeast are fungi and are more related to us than to bacteria. They have important applications in baking, brewing, and biotechnology. Yeast share many biochemical pathways with us and so by studying them, we can then extrapolate that to humans. In my lab we are working on glyphosate, the active ingredient in RoundUp, MCHM, a coal-cleaning chemical, and copper nanoparticles, a novel antimicrobial material.

What are your data and how do you obtain them?

I am an experimental geneticist. We have tens of thousands of different yeast strains in the lab. Most of these yeast come from other labs. The yeast community is generous, and these are all freely shared. To understand how RoundUp resistance occurs in nature, we also collect yeast from different environments. We have several sites with different RoundUp exposures. We started with a reclaimed strip coal mine, a state park, and the university organic farm. We have taken the public and students from local public schools to collect samples from these areas. We bring the samples to the lab and teach them how to coax the yeast out and then purify their DNA so we can sequence them. We thought that the mine would have the highest frequency of RoundUp resistant yeast because they spray that area every year with RoundUp. The park has been a state park since the 1930s and RoundUp was invented in the 1970s. RoundUp is a synthetic herbicide and not included in the list of herbicides and pesticides permitted on organic foods. We were completely shocked when we found that the organic farm had the highest number of RoundUp yeast and the mine had the fewest. There could be several explanations. One is that the yeast weren’t specifically resistant to RoundUp but whatever genetic changes that had been selected to gave it a selective advantage in that environment also conferred resistance. When we further investigated the histories of these sites we came up with another idea. The organic farm wasn’t always an organic farm. Two decades ago it was a conventional farm and from that previous exposure, the yeast became resistant and never lost it. The state park routinely uses RoundUp to combat invasive plants. There is also a power line that spans the canyon and they use helicopters to spray RoundUp so that trees don’t grow into the power line. The mine is used as a study site to find genes that are important for trees to grow on poor soil so that biofuels can be made. They started that study the year before I started collecting yeast so only a year of exposure was not enough to select for resistance. So now we have an even better study. We can go back every year to the mine and collect yeast. We can track RoundUp resistance as it happens.

How does your research contribute to the betterment of society in general?

We are exposed to and consume chemicals every day. Differences in how we respond to those chemicals in part depend on small differences in our genome. We use these genetic differences to find out how cells are metabolizing chemicals successfully and survive or unsuccessfully and die. When the human genome was sequenced, we thought that all its secrets would be unlocked. While tremendous advances in biomedical research could only have been done with this information, there is so much that we don’t know how to read. It’s like finally getting the keys to the entire library but all the books are written in a language that you taught yourself and they’re words that you don’t know how to translate. Based on a sequenced genome, we are not yet able to predict a person’s medical conditions or how a person will respond to drugs. The chemicals that we study are important agricultural and industrial chemicals. With the overuse of herbicides, we are now facing RoundUp resistant weeds. We don’t know how to combat this because we only partially understand how weeds become resistant. The active ingredient in RoundUp inhibits a biochemical pathway that plants, bacteria, and yeast have but humans do not. Therefore, it has been challenging to study possible effects of RoundUp exposure in humans. All known acute poisonings have been from the inactive ingredients and not the glyphosate. However, chronic exposure is time-consuming and complicated to study. We are using yeast to determine if there are other biochemical targets of RoundUp in yeast that humans may have. These studies can’t be done in plants because RoundUp exposure is lethal and prevents the synthesis of nutrients but yeast can be supplemented with the nutrients that RoundUp suppresses. Other chemicals like MCHM have limited toxicological information. Several years ago, a massive chemical spill contaminated the water supply in West Virginia. It caused headaches, nausea, and rashes and nobody knew why. MCHM changes how proteins fold and doesn’t have a specific target like RoundUp. By using this chemical we are studying how changes in protein folding regulate metal and amino acid levels in the cells. Fungal infections are difficult to treat because they are immune to antibiotics. Antibiotics work because they exploit fundamental differences in the metabolism of bacteria from humans. Yeast are more closely related to humans so there are fewer druggable targets. Copper is an effective antifungal material, but it is expensive, and metal has several drawbacks. By incorporating copper into cellulose-based nanoparticles, cheap, moldable, and biodegradable materials can reduce food spoilage and infections from medical devices.

What advice would you give to aspiring scientists?

Be prepared to fail. Failure is an opportunity to learn. In the example of the RoundUp resistance, the results were the opposite of what we thought. We can’t change the results, but we did further investigation and found an even more interesting story. I think of this as lost keys. My keys are always in the last place that I look. Why? Because I stop looking when I find them. If you think you know the answer, you stop searching. There is so much to discover and so many connections of which we are not aware. By challenging how you think about something you can overcome your assumptions and chip away at the unknown.

Head to Jen’s faculty page to learn more about her and her research by clicking here.

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