While Rachel Jones has wanted to do medical research since 3rd grade, it wasn’t until high school during her advanced placement class that she fell in love with the cell. “Cells are magnificent machines crafted by evolution, which is pretty cool considering evolution is progress derived [from] random events.” In particular, she remembers being completely fascinated with vesicles budding from membranes. “I took a research seminar my freshman year of college, and that’s how I found the Hollien lab,” she says. “I started coming in to [the] lab the fall of my freshman year to learn, and eventually I got to pursue my own mini project.” She’s been in the Hollien lab ever since and most recently was recognized as a Beckman Scholar, one of only two this coming year from the University of Utah.
The Beckman is an unprecedented opportunity, perhaps found nowhere else, in which an undergraduate researcher can hone their craft at the bench and under extraordinary mentorship. Funded by the Arnold and Mabel Beckman Foundation, the program is a 15-month, mentored research experience for exceptional undergraduate students in chemical and biological sciences. Each scholar receives a research stipend to facilitate nine academic calendar months and two, three-month summers of research experience.
Recipients from around the nation participate in the celebrated Beckman Symposium each summer with one another. Their research begins in June 2021 and will conclude in August 2022. Jones’s mentor is SBS Associate Professor Julie Hollien. Earlier Jones completed two semesters in the Undergraduate Research Opportunities Program (UROP) and received an Academic Excellence Scholarship. Not surprisingly, she has been on the Dean’s list every semester during her sojourn at the U and a member of the Phi Betta Kappa honor society.
Jones’s love affair with the cell is leading her back to her initial impulse to do medical research. She is currently absorbed in the lab with the degradation of mutant Huntingtin protein, implicated in Huntington’s, a fatal, incurable neurodegenerative disease. “Our lab discovered that the oligomeric form of this protein is degraded by a pathway that is not well studied. I aim to understand this pathway better by studying a protein I found to be involved.”
A hallmark of Huntington’s disease is the presence of large aggregates, which are composed of the mutant Huntingtin protein. And yet the mutant Huntingtin protein can also exist in a small, oligomeric form, that is composed of more than one subunit (polypeptide chain). “Interestingly,” says Jones, “it is thought that the oligomeric form is more toxic to the cells than the large aggregates. One idea is that the small form of mutant Huntingtin protein binds other structures in the cell and impedes their functions.” When the mutant protein is sequestered in the large aggregate, it can’t interfere with cellular functions. “This is one model for how the smaller form of the mutant Huntingtin protein is more toxic,” she says.
A native of Albuquerque, New Mexico, Jones found an early mentor in Jess Mella, now a graduate student at University of California, San Francisco. “She was amazing to learn from,” says Jones, “because she is brilliant and loves what she does …. I am inspired by her passion and drive for science, and I’m grateful I was able to get to know her and learn from her when I was starting out on my research journey.”
That journey for Jones includes a love for organic chemistry (an honors student, she is minoring in chemistry). Currently, she’s a teaching assistant in “Ochem” and is looking forward to taking a protein chemistry class this fall. Typical of the integrated nature of the School of Biological Sciences’ many research interest areas, she also took a field botany course. “I love being able to identify different plants when I go hiking,” she says.
Jones loves trail running and summiting peaks, so Utah is a prime location for her. And during the pandemic, she and her roommates fostered three cats, a service she found rewarding. She also temporarily took a job at Café Zupas, a food emporium in downtown Salt Lake because when the pandemic started, undergraduates were not allowed in the labs for a time. That has since changed, and she’s now back in the lab with her Beckman mentor Julie Hollien whose lab’s overall goal is to understand how cells deal with stress by controlling organelle trafficking and protein and mRNA turnover.
Rachel Jones hopes to apply to PhD programs for biology this fall. “I would like to have a career in biomedical research. I’ve always wanted to contribute towards developing a cure for a disease. That’s one of the reasons why I’m excited about my project: it has a medical application. …Sometimes I think to myself: I’m so lucky I can pursue a career in something so cool and interesting.”
- Role of p62 in alternative degradation of Huntingtin protein (R. Jones)
Huntington’s disease is a fatal, incurable neurodegenerative disease characterized by protein aggregates in the brain. These aggregates result from an accumulation of the mutant form of the Huntingtin protein (mHTT). Initially, the mHTT exists in the form of small, soluble oligomers, but eventually, it forms large aggregates. Surprisingly, the small oligomers are thought to be more toxic for the cells than the large aggregates. The cells have pathways to degrade the mHTT, but they are overwhelmed in the disease state. The degradation of the large aggregates is well characterized, but the alternative pathway by which the small, more toxic oligomers are degraded is not well understood. My preliminary data suggest that the protein p62 is involved in the degradation of these mHTT oligomers. It is unknown how p62 functions in this degradation pathway. My project aims to test several hypotheses of how p62 contributes to the degradation of the small, toxic oligomers of mHTT. I will identify the domain(s) of p62 necessary for its function in the pathway, any potential p62 binding partners, and point in the pathway at which p62 functions. I will study p62 using siRNA knockdowns, flow cytometry and microscopy in a cell culture model of Huntington’s disease. By improving our understanding of the degradation pathway of the toxic mHTT oligomers, we may be able to enhance the pathway as a therapeutic to combat Huntington’s disease. Clarifying the role of p62 will give us a better understanding of the pathway and a potential target for therapy.