Abstract: Cells respond to stress by mounting a response to maintain homeostasis. It is currently unknown how cells sense and respond to the stressful condition of lipid depletion. Previous work in the lab found that knock down of the transcription factor, hsf-1, in C. elegans caused Rab GTPase dissociation from vesicles, significant fat loss and a 100 fold increase in rab-11.2 transcription. Rab proteins attach to vesicles via two geranylgeranyl (20 carbon) lipid moieties made through the isoprenoid pathway. RAB-11.2 has never been functionally characterized yet it has a 74% sequence similarity to RAB-11.1, which is involved in recycling endosomes. Here, we used worm fat stains and fluorescent reporters to uncover a novel, inducible Rab mechanism activated under impaired metabolic conditions. We hypothesize that defects in the isoprenoid pathway prevent RAB-11.1 from binding to vesicles and freeing the transcription factor, NHR-49, to translocate into the nucleus. This activates a transcriptional response that activates rab-11.2 expression, nutrient transporters and fatty acid beta oxidation genes to promote nutrient absorption and energy production to rescue the animal in starved conditions. Email:[email protected]
What Does Research Mean To You? Research is the intellectual journey that we undergo in order to solve pressing problems. Just like any other journey it is facilitated through collaboration and learning from others. Research also gives me the freedom to investigate what I find interesting and directly answer the questions that I have. Tell Us About Your Journey I started out my research journey with little idea about the magnitude of depth researchers go through. I started out doing simple lab tasks and experiments which was fun especially when analyzing my results. However, the real work lies in designing and fine tuning these experiments as well as coming up with questions and hypotheses. I am working hard at this part by making sure I understand each part of the design and how it helps me answer my ultimate question. I also continue to do literature searches to identify gaps in knowledge which help to further my project.
How Did the Pandemic Affect Me? The pandemic gave me a new perspective on the research process. When the semester started, I was working on an ongoing project that had been fleshed out pretty well. After the shutdown, we began thinking about new questions and projects which gave me insight into the critical thinking necessary for nascent stages of research. I saw how scientists link ideas, data and publications to propose a story. We also brainstormed assays and techniques to best accomplish our aims. The pandemic accelerated my learning of these necessary skills with hands-on, albeit virtual, training.
Where am I now? Have started in the MD/PhD program at UT Southwestern.
Advice for Future Green Fellows
Don’t be afraid to try something new. This can be in brand new subject areas, topics or even assays but there is something special of stepping out of your comfort zone. Although it will be difficult in the beginning, reading up on new terms, asking questions, and doing the experiments will help you learn and expand your breadth of knowledge. It also helps to review salient items multiple times to keep refreshing your memory. Don’t feel discouraged and keep at it; soon everything starts to make sense.