Research Background

Dr. Emily Troemel, Associate Professor at UCSD

Dr. Emily Troemel, Associate Professor at UCSD

Dr. Emily Troemel is an Associate Professor of Biological Sciences at UC San Diego. As a graduate student, she discovered and characterized the first identified chemosensory receptors in C. elegans (roundworm). Next, she helped launch a start-up biotech company for four years. After this company went public, Dr. Troemel returned to academic research as a postdoc, where she identified the first natural pathogen of C. elegans named Nematocida parisii. This pathogen defines a new genus and species of microsporidia, which are priority pathogens of medical and agricultural significance. Microsporidia can be found in water supplies and can cause a variety of infections, known as microsporidiosis, which affect people with weakened immune systems. The parasites can infect the lungs, kidney, brain, muscles, eyes, sinuses, or intestines, and can cause gallbladder disease and a debilitating array of gastrointestinal symptoms, including chronic diarrhea.

Dr. Troemel’s lab uses the natural host/pathogen system in C. elegans to determine how microsporidia cause disease. In her seminar at the Buck Institute, she first talked about how worm intestinal cells are invaded and hijacked by Nematocida parisii. In addition to microsporidia, she also talked about host response to infection by the bacterial pathogen P. aeruginosa. Her lab’s key findings indicate that P. aeruginosa-delivered toxins trigger host defense signaling in C. elegans. Additionally, P. aeruginosa infection inhibits mRNA translation in the worm intestine via the endocytosed translation inhibitor Exotoxin A, which leads to an increase in zip-2 protein. Dr. Troemel identified the transcription factor zip-2 as a key player in the inductive response in C. elegans to infection with P. aeruginosa. Ultimately, she discovered that zip-2 mediates the induction of a discrete subset of infection response genes in C. elegans and is important for defending against P. aeruginosa infection.


Q: Do ZIP-2 mutant worms live for less time when they are infected with P. aeruginosa?

ET: ZIP-2 was identified as a transcription factor that is required for inducing infection response [defending against the infection]. It can also promote defense response: if you either knock down ZIP-2 with RNAi or if you look at ZIP-2 mutants, they are susceptible to infection. So they have shorter lifespans after infection [compared with uninfected worms]. Wild type worms will die pretty quickly with P. aeruginosa infection but ZIP-2 mutants die even faster.

Q: Do the pathogens deliver different toxins? If so, do they go through the same mechanism?

ET: There is a big diversity of toxins that are delivered by P. aeruginosa or other pathogens. I focused on Exotoxin A, because you can link an attack by this pathogen with certain phenotypic response in the host. But there are other protein-based toxins as well as small molecule-based toxins. And one of the major points that we are trying to convey is that toxins can have many different structures. So molecularly, they are quite different from one another, but they regulate common processes. Targeting mRNA translation, mitochondria, or the proteasome, are a few examples.

Q: Is the toxin triggered zip-2 mechanism conserved in mammalian organisms?

ET: Yes. ZIP-2 doesn’t have a direct ortholog (genes in different species that have the same function), but there is a binding partner of zip-2, which is called CEBP-2. CEBP-2 is an ortholog of CEBP-γ (CCAAT-enhancer-binding protein γ). We have some unpublished data suggesting that CEBP-γ in mammals is doing something similar to what CEBP-2 does in worms.

Q: Can you talk a little about the therapeutic strategy for infection treatment?

ET: I think the therapeutic strategy could be to find a way to boost the detection mechanism of toxins, so we will have a stronger response against infection. For example, cystic fibrosis patients can get chronic pseudomonas infection. If CCAAT-enhancer-binding protein is the key, we can target it with drugs to make it more effective and thus turn on more defense gene expression.

Q: How does host/pathogen interactions have an impact on the aging field?

ET: Our major focus is to understand how pathogens exploit the host, and how hosts defend themselves. We are not working on aging per se, but there are a lot of pathways that are important for resistance to infection that also play a role in aging and healthspan. We are looking at the response to intracellular infection, and we found that these responses are regulated by proteostasis function. We got this very interesting worm mutant that is resistant to pathogens and also resistant to heat stress. This mutant also has phenotypes that you can observe in the long-lived mutants. So if we can find out pathways that can help the animal better deal with stress, we think it will also be helpful for healthspan.

Q: You went to a start-up for a couple of years. How do you like working at a start-up and in industry?

ET: I was very fortunate to have an opportunity to join this company. It was a small neuroscience based company. I think the benefit of being at a start-up is that I could wear many hats. I could work on a lot of areas like gene expression analysis, neuronal identity, establishing important foundations for drug development, drug screening and mechanism of action studies. I got to work on a whole bunch of different questions because start-up companies often change directions. Our company ended up switching to be a more of a neuro-inflammation company, so I learned a lot about inflammation and immunity. So in a small company, you can move around a lot. And the company grew quite a bit. There were over 100 people after a short period of time. I was one of the first scientists who joined the company. There were only about 15 people when we started.

Q: Why did you come back to academia after 4 years in industry?

ET: At the end, I realized that I missed basic science questions. Because in a company, everything we focused on was getting a drug developed, and things are profit driven. There is little motivation to share what you are doing in the early days. I really like that in academia you can share your data. You can go to a conference to talk about your unpublished data and get feedback. I also think it is really important to work on basic science, because in the end, it’s where the ground breaking discoveries come from. For instance, you’re hearing in news these days about CRISPR/Cas9, and how this technology is being used as a genome editing tool. CRISPR/Cas9 did not come from someone who was trying to treat diseases; it came from someone who was trying to understand the immune system of bacteria. Who on earth would think that this system could have such a huge application? Transforming basic science discoveries and translating them to treatment for disease is very important. But I am very excited and motivated about basic science questions. So that is why I ultimately returned to academia.

For more information on Dr. Troemel or her exciting research, check out the Troemel Lab Website!