Rachel Jones

Rachel Jones

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.

Doing a staining experiment, using a GFP antibody to visualize the mutant Huntingtin protein.

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.

Atop Lone Peak at the edge of Little Cottonwood Canyon.

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.”

Beckman Abstract

  • 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.

 

Diana Montgomery

Diana Montgomery


“Perhaps my favorite experience at the University of Utah is when I started working in a biology lab for the first time and realizing I fit in and enjoyed the work and the people there,” says Diana Montgomery, BS’87 in Biology. “It certainly helped to solidify my career choice.”

While at the U, Diana worked in Allen Edmundson’s crystallography lab on Wakara Way. In addition to learning practical skills, Diana was included in the research publication, titled “A mild method for the preparation of disulfide-linked hybrids of immunoglobulin light chains” in 1987. The journal was Molecular Immunology. (Read the paper here.)

Shortly thereafter, Diana graduated from the U and moved to Baltimore, Maryland, to begin graduate school at Johns Hopkins University. Her advisor was Ernesto Freire, a well-known expert in biological thermodynamics. Diana completed a doctorate degree in Biology/Biophysics from Johns Hopkins in 1994 and conducted postdoctoral work at Northwestern University in the lab of Richard Morimoto and at the University of Massachusetts in the lab of Lila Gierasch.

Diana is now a Principal Scientist in the department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism at Merck, in Pennsylvania. She focuses on developing therapeutic proteins as new drugs, two of which are now FDA-approved products, tildrakizumab and bezlotoxumab.

Tildrakizumab (brand name Ilumya) is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis in the United States and Europe. Tildrakizumab is a monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

Bezlotoxumab (brand name Zinplava) is a monoclonal antibody designed for the prevention of recurrence of Clostridium difficile infections, which can be life-threatening. Bezlotoxumab works by binding to a specific toxin produced by the Clostridium difficile bacteria and neutralizes the toxin’s effects.

Merck is a multinational company and one of the largest pharmaceutical companies in the world, employing some 74,000 people. In 2020 alone, Merck invested $13.6 billion in drug research and development.

Diana has 24 research publications with nearly 1,400 citations to her credit. Her recent work has focused on describing the effects of immunogenicity on therapeutic proteins. One liability of protein-based therapeutics is their tendency to elicit an unwanted immune response against themselves. One of the manifestations of such an immune response is the activation of B cells, which produce anti-drug antibodies that bind to therapeutic protein drugs and can reduce a drug’s therapeutic effects or be associated with safety issues. Therefore, an important part of therapeutic protein drug development is to characterize the tendency of a drug to elicit anti-drug antibodies and any potential effects on clinical pharmacokinetics, efficacy, and safety.

Reflecting back to her childhood, Diana recalls several key moments that motivated her to study science.

“My father was a mining engineer. He did some geology education while we were hiking, like what type of rocks were on the trail and how to recognize fool’s gold,” says Diana. “When we went camping, he’d explain the Pythagorean theorem with the triangles of the tent. It made math and science familiar to me.”

In high school, Diana developed an interest in molecular biology and biochemistry. She then chose to attend the University of Utah because it was a reputable research university which was close to home. (Diana grew up in Tooele, Utah, about 30 miles from the U.) Diana received an Honors at Entrance scholarship to begin her studies at the U, based on her achievements in high school.

“At the U, several classes in the Department of Biology (now School of Biological Sciences) were designed to encourage students to make and test hypotheses. This form of experimental-based learning was both effective and highly enjoyable,” said Diana.

“Professors like Gordon Lark and John Roth were fantastic. They made their lectures interesting and taught us how to think like a scientist and how to do science in the laboratory. I was lucky to be a part of that, but at the time didn’t realize it was so rare. I believe it is important for students to get a feel for doing science in introductory classes like these, rather than being exposed to it for the first time in graduate school. By the end of my undergraduate years, I was hooked on the scientific paradigm of hypothesis, design, experiment, and interpret. I have the U to thank for that.”

Diana and her husband, Hwa-ping (Ed) Feng have two children, Ellen and Nathan. Diana particularly enjoys gardening and reading. She also volunteers at a local food pantry and at animal-adoption clinics.

The College of Science and its four academic departments – Biological Sciences, Chemistry, Mathematics, Physics & Astronomy – now graduate more than 650 students each year. We are proud of our many alumni who live and work all around the world. Please share your stories with us!

Are you a Science Alumni? Connect with us today!

Advising & Registration

Advising & Registration


Now that you have completed your New Student Virtual Orientation modules, you will be able to register for an advising and registration session. Use the links below to register.

August 10 at 2 pm 

August 11 at 10 am 

August 12 at 2 pm

Prepare for Your Advising Session
  • Make sure your FERPA pin is set up
  • Check out the Math Placement website and come with an idea of what math class you think you should be in (a list of the math classes you took in high school is also helpful here)
  • List of AP/IB classes taken and the scores you received on tests
  • Think about the goals you have for your first semester
  • Come ready to participate and ask any questions you have so far!
    • What gen eds are most helpful for my degree?
    • How do I build my class schedule around my job?
Attend Your Advising Session
  • This is where your advising hold will be removed so that you can register for courses
  • Learn more about the College of Science and your department
  • Meet one-on-one with an Academic Advisor for quick first semester course planning (you will not receive a four year plan at Orientation)
  • Learn how to use Schedule Builder
  • Register for Fall 2022 classes!

Let’s Get Kraken

the sigman Group launches open-access tool for chemists


An open-access tool for chemists that promises to save time and money in the discovery of chemical reactions has been launched this week by the research group of Distinguished Professor Matt Sigman of the University of Utah Department of Chemistry and the Matter group of professor Alán Aspuru-Guzik at the University of Toronto.

Kraken—created in a collaboration between the Matter lab, the Sigman group, IBM Research and AstraZeneca—is a library of virtual, machine-learning calculated organic compounds, roughly 300 thousand of them, with 190 descriptors each.

“This collaborative project changes how researchers will approach reaction optimization both in industry and academics,” Sigman says. “It will provide unforeseen opportunities to investigate new reactions while also the ability to know why the reactions work.”

“The world has no time for science as usual,” says Aspuru-Guzik, “Neither for science done in a silo. This is a collaborative effort to accelerate catalysis science that involves a very exciting team from academia and industry.”

“It takes a long time, a lot of money and a whole lot of human resources to discover, develop and understand new catalysts and chemical reactions,” says co-lead author and Banting Fellow Dr. Gabriel dos Passos Gomes. “These are some of the tools that allow molecular scientists to precisely develop materials and drugs, from the plastics in your smartphone to the probes that allowed for humanity to achieve the COVID-19 vaccines at an unforeseen pace. This work shows how machine learning can change the field.”

When developing a transition-metal catalyzed chemical reaction, a chemist must find a suitable combination of metal and ligand. Despite the innovations in computer-optimized ligand design led by the Sigman group, ligands would typically be identified by trial and error in the lab. With kraken, chemists will eventually have a vast data-rich collection at their fingertips, reducing the number of trials necessary to achieve optimal results.

The Kraken library features organophosphorus ligands, what Tobias Gensch—one of the co-lead authors of this work—recalls as “some of the most prevalent ligands in homogeneous catalysis.”

“We worked extremely hard to make this not only open and available to the community, but as convenient and easy to use as we possibly could,” says Gomes, who worked with graduate student Theophile Gaudin in the development of the web application. “With that in mind, we created a web app where users can search for ligands and their properties in a straightforward manner.”

The team also notes that while 330,000 compounds will be available at launch, a bigger-scale library of over 190 million ligands will be made available in the future. In comparison, similar libraries have been limited to compounds in the hundreds with far fewer properties.

“This is very exciting as it shows the potential of AI for scientific research,” says Aspuru-Guzik. “In this context, the University of Toronto has launched a global initiative called the Acceleration Consortium which hopes to bring academia, government, and industry together to tackle AI-driven materials discovery. It is exciting to have Professor Matthew Sigman on board with the consortium and seeing results of this collaborative work come to fruition.”

Kraken can be freely accessed here. The preprint describing how the dataset was elaborated and how the tool can be used for reaction optimization can be accessed at ChemRxiv.

Story originally published in @theU

Tour the College of Science

Tour the College of Science


Tour the stunning science campus at the University of Utah with two of our Science Ambassadors, and learn more about the opportunities available to our students.

  • Register below to schedule a tour at a time that is convenient for you and your family
  • Tours begin at the Crocker Science Center on Presidents Circle
  • Plan for your tour to last about one hour with plenty of time to ask our Ambassadors and COS staff questions about student life, classes, and more!

 

Tours are closed for the summer. Check back in the fall to tour the College of Science.

 


What you can learn from a tour


Camille-Dreyfus Award

Luisa Whittaker-Brooks recognized with the Camillle-Dreyfus Teacher Scholar Award


Luisa Whittaker-Brooks, an assistant professor in the department of chemistry, is among 16 early career chemists named as a 2021 Camille Dreyfus Teacher-Scholar. Selected by the Camille and Henry Dreyfus Foundation, Camille Dreyfus Teacher-Scholars receive an unrestricted $100,000 research grant.

“I was actually having a meeting with my undergraduate students when I received a text message from my Ph.D. advisor with the news,” Whittaker-Brooks says. “The only thing I could think about after the text was how instrumental my undergrads were in getting this award.”

Camille Dreyfus Teacher-Scholars, according to the Dreyfus Foundation, “are within the first five years of their academic careers, have each created an outstanding independent body of scholarship, and are deeply committed to education.”

Whittaker-Brooks’ award cites her research in “designer hybrid organic-inorganic interfaces for coherent spin and energy transfer.” Her research group, their website says, is “driven by two of the greatest challenges of our time –sustainable energy and low cost electronics for daily use applications. We plan to embark in these new endeavors by synthesizing and elucidating the functional properties of well-defined and high-quality materials for applications in photovoltaics, thermoelectrics, batteries, spintronics, and electronics.”

Story originally published in @theU