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.

 

Sahar Kanishka

Undergraduate Research Award


Sahar Kanishka

Biology major receives 2021 Outstanding Undergraduate Researcher Award.

Sahar Kanishka remembers daily where her family came from, where they are now, and what opportunity there is for her at the School of Biological Sciences (SBS).

“I’ve always wanted to be a doctor ever since I was younger,” she recently explained in a video interview. “Because my family’s from Afghanistan and they actually fled from the Soviet invasion, they were telling me how the medical resources over there were very scarce when they were escaping. Like things we take for granted here [in the United States]. I want to be able to give back in some way. And that’s my way of giving back, becoming a doctor and contributing what I’ve learned here.”

What Kanishka, now in her junior year as an honors student, is learning happens largely in the Gagnon lab at the SBS where she and her colleagues are studying vertebrate lineage and cell fate choice along with cell signaling and genome engineering. Their subject model is the living zebrafish with which they are attempting to answer the question of how biology builds an animal with millions of cells. The question is complicated by the fact that those millions of cells are continually sharing information while shape-shifting at the same time.

Zebrafish

A living organism is the culmination of science turning chaos and cacophony into a kind of marvelous symphony. Using CRISPR-Cas9 gene-editing technology, the Gagnon lab is busy marking cells with a genetic barcode that could later be used to trace the lineage of cells that in the zebrafish are similar to other vertebrates, including humans.

The micro “scissors” of CRISPR is no longer just being used to decode the genome, but to make a version, readable to humans, of what cells are doing in real time and how. It’s research that’s contributing to a sea change in genomic studies, and Kanishka is there at the bench experiencing it firsthand. The way Jamie Gagnon, Principal Investigator who holds the Mario Cappechi Endowed Chair at SBS, puts it, the research Kanishka is doing “may lead to a holy grail method for developmental biology—the ability to record developmental history, in living animals, with molecular and spatial resolution.”

Little wonder then that the Undergraduate Research Program at the University of Utah chose Kanishka for this year’s award. In his nomination letter Gagnon, who referred to Kanishka as having “transitioned quickly into an independent scientist," also wrote that he has been “impressed with Sahar’s poise, focus and commitment to research over the last year, which has been particularly challenging for our undergraduate researchers… . Sahar is already the face of STEM research in the College.”

Kanishka’s journey at the U threaded through ACCESS, a signature program of the College of Science. It was a scholarship and mentorship experience that led to re-figuring what research could be. Instead of working primarily on a computer in isolation and doing anatomy lessons from a book, ACCESS and SBS provided her with a hands-on approach in its full cadaver lab. As a pre-med student hoping to earn a joint medical degree and doctorate, Kanishka’s turn as a teaching assistant to professor Mark Nielsen gave her added invaluable experience. ACCESS also gave her a practical skill set, like creating her first research poster and then presenting it publicly.

The ACCESS program

The same has been true in the Gagnon lab where she says you are free to mold your research experience to your own expectations. Research at the U “fosters an environment of curiosity of real research. It’s really beautiful,” she says, “to have someone [like Gagnon] believe in you like that.” This, she concedes, in spite of feeling at times like an imposter as the child of an immigrant family and as a woman. She’s had to “learn through lots of struggles.”

Some lessons from those struggles have been hard won. “You can’t just put science in a box and tell it what to do,” she explains. “I have to allow it the freedom to seek to understand the world rather than to just understand me.” Her joint undergraduate degree in business administration speaks to Kanishka’s sense of the intersectionality of all learning. She was especially impressed with a recent visit by Reshma Shetty, the inaugural SBS Distinguished Lab Alumni who worked with Baldomera “Toto” Olivera in his lab and is a co-founder of Boston-based Gingko Bioworks, a bio-engineering start-up.

But the ballast in Kanishka’s life--both that of her academic career’s and that of her personal story’s--continues to be family. That includes not only her younger sister and parents here in Utah, but also her extended family in Afghanistan and beyond. “I hate that we’re separated by distance,” she says, referring to her overseas cousins, aunts and uncles as “my other parents and siblings. I owe everything to them. They mean everything to me.”

Until she and her extended family are all at least on the same side of the globe, Kanishka has both advice and a caution for her undergraduate colleagues. “Figure out if you want to do something by actually doing it,” she advises, recommending internships for high schoolers not bound for college, including through a program she helps facilitate as a volunteer called Talent Ready Utah. “College can be a business,” she warns, “pumping out students” for a job market they may not resonate with or even prosper in.

But Sahar Kanishka is optimistic about things as well. When asked about the pandemic and the social and economic upheaval, she proffers a winning smile, while adding, “I’m excited to see how college will change and adapt.”

 
by David Pace
 

Beckman Abstract

  • Lineage tracing in zebrafish with CRISPR prime editing (S. Kanishka)
    All embryos develop from a single cell. We use lineage tracing to map the relationships between individual cells and back to the initial founding cell. These lineage trees can help us understand how cells acquire their fates during normal development, and how that can go wrong in human disease. An emerging method for lineage tracing in embryos uses cellular barcodes. Cellular barcodes individually tag cells with a unique set of mutations specific to that cell. As cell divisions occur, the barcode is passed on to the progeny cells and a lineage tree can constructed based on cells that share similar barcodes. The CRISPR-Cas9 system for gene editing is an ideal tool for creating a huge diversity of cellular barcodes in embryos. However there are limitations with CRISPR-Cas9, including unpredictable indel formation and difficulties in recovering barcodes from cells. In this project, a modified CRISPR system known as prime editing will be applied in zebrafish, and utilized for lineage tracing. Prime editing allows for precise genome editing by inserting user-specified genetic sequences at a target site in the genome. I hypothesize that we can use prime editing to insert a huge library of user-specified barcodes into the genome of developing zebrafish. Because these barcodes are defined by the experimenter, they can be recovered at the end of the experiment using RNA in situ hybridization. In principle, lineage tracing with prime editing will allow us to discover the spatial arrangement of related cells in intact embryos and tissues. We hope to use lineage tracing with prime editing to understand the mechanisms of heart regeneration in zebrafish.

Sonia Sehgal

Sonia Sehgal

 

U Biology's Sonja Sehgal accepted a Beckman Scholarship this past spring to add to the trove of awards that were already sitting on her academic “mantle” at home. Collective kudos include a Biology Research Scholars Award, a College of Science Scholarship and a Utah Flagship Scholarship.

The Beckman, however, is a step up from her other awards. It represents an unprecedented opportunity, perhaps found nowhere else, in which an undergraduate researcher can hone her craft at the bench and under extraordinary mentorship. The program is a 15-month, mentored research experience for exceptional undergraduate students in chemical and biological sciences, and Martin Horvath, associate professor in the School of Biological Sciences, will serve as her mentor. (Rory Weeks, undergraduate in the Department of Chemistry is the second U Beckman Scholar for 2020-21.) Each scholar receives a $21,000 research stipend to facilitate nine academic calendar months and two three-month summers of research experience. Recipients from around the nation participate in the prestigious Beckman Symposium each summer with one another. Their research began in June 2020 and will conclude in August 2021.

“I started out as a freshman in the ACCESS,” the biology senior explains, referring to the decades-long program hosted by the College of Science Program for Women in Math and Science. “Through this program, I was able to explore various fields in STEM which really kick-started my interest in pursuing biology! Joining the Horvath Lab further sparked my curiosity and has shown me that science goes beyond the stereotypical image of a “scientist.”

Tracking toward a career in medicine

Sonia Sehgal (undergraduate, Biology Research Scholar, Beckman Research Scholar) and Martin Horvath discuss the structure of MutY

Sonia Sehgal (undergraduate, Biology Research Scholar, Beckman Research Scholar) and Martin Horvath discuss the structure of MutY.

Sehgal is far from stereotypical, as a scientist or as an undergraduate. As a woman she knows that she’s in the minority as she works through her academic career and finally a professional career in STEM (Science Technology Engineering and Mathematics). As a complement to her academic career, the Sandy, Utah native has found a job as a University Ambassador. “The ambassadors work closely with the Office of Admissions to share our experience and bring a personal perspective to prospective U of U students,” she says. “When not giving tours or working recruitment events, we can be found having a good time with each other or,” she quips, “practicing walking backwards.”

Though Sehgal finds herself walking backwards while giving tours, she is definitely moving forward in her academic career. “I’m excited to continue doing research and I also plan on attending medical school after graduation. I want to learn about the various mechanisms that can cause diseases to present themselves in different forms across individuals. I want to use this platform to relay these findings with patients and create more representation in the field to strive for a more trusting and effective patient interaction.”

But before medical school, there’s research to be done, a focus in undergraduate education in the SBS that has arguably become the School’s signature.  “In the Horvath lab,” Sehgal explains about her work, MUTYH is a DNA repair enzyme commonly related to diseases like cancer. I am currently finding the role of different biological probes to see how they can affect the activity of this enzyme. Learning more about regulating the activity of MUTYH will allow us to create better drug-targeting systems for cancer in the future.” What most people, even the scientifically-inclined, may not know about the model subject Sehgal is studying is that the MutY enzyme can be found in almost every living organism, yet there is still a lot we don’t know about it.

Hangin' out.

That’s something that inspires rather than discourages Sehgal who will graduate with her BS in 2021. With the help of the Beckman Scholarship, the mentorship of Horvath and the broad view of higher education she gets by being an ambassador, Sehgal finds her future as she tracks toward a career in medicine, promising. And true of all of accomplished undergraduate researchers of Sehgal’s stripe, she is poised for far more awards, and accomplishments.

“The Beckman experience has been going well,” she reports. “Because of the COVID-19 pandemic, the first stage has been virtual. I have been working on coding and molecular docking. However, I look forward to getting into the lab next semester and start testing!” Of Sehgal Horvath adds, "Sonia has a gift for finding a simple clear question to address in her science. She will go far. I feel really lucky to have had the chance to work with her these past years."

Asked what her interests and “likes” she doesn’t stray very far from her time in the lab. She likes rock climbing, dogs … and getting positive results for polymerase chain reaction (PCR), a method widely used to rapidly make millions to billions of copies of a specific DNA sample.

It’s the sort of thrill that allows a budding scientist, like Sonia Sehgal, to take a very small sample of DNA and amplify it to a large enough amount to study in detail.

Beckman Abstract

  • "Finding the role of biological probes on MUTYH activity,"(S. Sehgal)
    DNA damage is implicated in many cancers, such as colorectal cancer. One form of this damage occurs when guanine becomes oxidized to form 8-oxoguanine (OG). MUTYH is a base excision repair (BER) enzyme in humans that excises adenine (A) at OG:A lesions in DNA and thus prevents mutations that may arise after rounds of replication. Interestingly, both inhibition and overactivation of MUTYH can contribute to cancer-causing activity. In this project, MUTYH will be studied through computational modeling and an activity assay to find biological probes that can bind to the protein and affect its function. These probes can later be tested in animal models and may serve as the foundation for anticancer drug discovery. In addition, through analyzing the effect of biological probes on this enzyme, the BER pathway and the dual role of MUTYH in preventing and causing cancer can be further understood. Use of these probes to control MUTYH activity and BER overall can aid with creating more efficient drug targeting systems for cancer treatment in the future.

 

 

by David Pace

 

 

Rory Weeks

Rory Weeks

Beckman Abstract

  • Mechanistic understanding of a model solid electrolyte/electrode interface for advancing electrochemical energy storage applications (R. Weeks)
    To mitigate the impacts of anthropogenic climate change as we transition from fossil fuels to renewable energy, advanced storage systems are necessary to make intermittent renewable energy sources a viable option. One solution for meeting these energy storage needs involves the use of batteries. However, the lithium-ion battery technology ubiquitous in electronic devices and electric vehicles may be unsuitable for advanced grid storage systems due to concerns about lithium sourcing and safety. In particular, safety issues stem from the use of flammable liquid organic electrolytes and the formation of a poorly defined solid electrolyte interphase which can deleteriously affect battery performance. My research will investigate beyond lithium-ion battery and liquid organic electrolyte technologies in favor of all solid-state sodium batteries. My objective is to develop a multimodal approach to determine the key characteristics of solid/solid interfaces, tailored with controllable interlayers chosen to mediate ion/charge transfer between a nanowire cathode and ionically conducting polymer electrolyte. Such understanding will enable the fabrication of highly efficient and environmentally safe beyond lithium-ion energy storage technologies with tunable interfaces.

 

Ming Hammond

A Conversation with Dr. Ming C. Hammond

Meet Dr. Ming Hammond, one of the members of the inaugural class of Beckman Scholars, and read her thoughts and perspectives regarding the personal impact of the program on her undergraduate experience and resulting career.

Then: 1998 Beckman Scholars Program Award Recipient, California Institute of Technology

Now: Assistant Professor of Chemistry and Molecular & Cell Biology, University of California, Berkeley

“The support of my research mentor and the Beckman Scholars Program gave me the confidence and the skills to pursue an academic and research career.”  

AMBF: Prior to college, were you curious about a career in science?

Ming Chen Hammond (MH): Yes.

AMBF: What exposure did you have to knowing what research in a laboratory would be like? 

MH: As a high school student, I spent a summer commuting into Baltimore city to shadow researchers in a lab at UMD Baltimore medical center that worked on studying the mu opioid receptor.

AMBF: When you heard about the Beckman Scholar opportunity, what inspired you to apply? 

MH: My research advisor, Barbara Imperiali, told me about the program and encouraged me to apply.

AMBF: What was your research focused on? What were the results? 

MH: For the Beckman Scholar application, I conceived of an independent project to identify the active site subunit of the enzyme, oligosaccharyl transferase, by synthesizing a peptide inhibitor carrying a biotin affinity tag and a metal-chelating sequence that Thomas Kodadek had shown could be used for site-specific crosslinking. It turned out that this project was a “chemical biology” project, before I had even heard of the field of chemical biology. As a Beckman Scholar, I carried out the chemical synthesis, the enzyme purification (from fresh pig liver delivered from a farm!), the activity assays, then the crosslinking experiments to ID the active site. We didn’t publish the results, but years later I read a paper that confirmed my results using a different method. I won the Caltech SURF (summer undergraduate research fellowship) speaking competition for my talk about this work, the chemistry department award (Arie J. Haagen-Smit Memorial award) for my research, and I received a Howard Hughes Medical Institute predoctoral fellowship (that I accepted) and National Science Foundation graduate fellowship (that I declined). I was also featured in a Time magazine article about Caltech at the time.

AMBF: What was the most memorable part about working with your mentor or working in the laboratory? 

MH: Again, what was unique about my research experience as a Beckman Scholar was having an independent project. When my mentor moved to MIT in the summer before my senior year, the Beckman Scholarship allowed me to spend 10 weeks in Cambridge, MA to finish my project. Moving to a new city and a new institution opened my eyes a lot, even before grad school.

AMBF: How did the experience change your thinking about science and conducting research? 

MH: This experience was the first time that I had the freedom and the opportunity to conceive of and execute my own research idea. This was very empowering, and I realized that independent research was what I want to do the rest of my life, and it solidified my desire to become a professor. Also, many of the ways I run my lab is inspired by the level of organization and the camaraderie I experienced in the Imperiali lab.

AMBF: Where did you go after graduation and where are you now?  

MH: I went to the Chemistry Ph.D. program at UC Berkeley.  I am currently an Assistant Professor in Chemistry and Molecular & Cell Biology at UC Berkeley.  I am recipient of the BWF Career Award at the Scientific Interface and the NIH Director’s New Innovator Award.  My lab develops assays that are useful for high-throughput drug screening inside and outside of cells, and we apply these assays to understand how chemical signals affect bacterial behavior. I have published many papers and have applied for patents, several of which are licensed or under evaluation for licensing.

AMBF: Do you have any advice for undergraduates considering a research career? 

MH: I have advised and mentored a lot of undergraduates, as majors advisor, teacher, and research advisor. For those in other research labs, I gently push them to talk with their professor at least once a semester. For those in my research lab, I encourage them to consider coming up with their own projects after they have learned the ropes.

AMBF: Did you meet Dr. Beckman in person, and if so, what was most memorable about meeting him?

MH: I met Dr. Beckman in person at the first Beckman Scholar Symposium.

AMBF: Any final thoughts? 

MH: I just want to express my tremendous gratitude and appreciation to Dr. Beckman, his family, and the Scholars program. The support of my research mentor and the Beckman Scholars Program gave me the confidence and the skills to pursue an academic and research career.

> Original Article Beckman Foundation Interview - 2017