The 2025 R. Bryan Miller Symposium brought together students, faculty and multiple Nobel laureates to share and advocate for scientific research
By NAREN KRISHNA JEGAN
From March 6 to 7, the UC Davis Department of Chemistry held its annual Miller Symposium, a conference where undergraduates, graduate students and guest speakers share their current research interests and findings through talks, poster presentations and flash pitches. Named after the late Professor R. Bryan Miller, this year’s symposium featured some recognizable figures within the chemistry community, such as Nobel laureates Jennifer Doudna and Frances Arnold, as well as internationally renowned pioneers such as Dr. Kendall N. Houk, Alanna Schepartz, Dirk Trauner, Laura Kiessling, Ashok Bhandari, Wendy Young, Sundeep Dugar and Michael Marletta. In addition, multiple faculty members (Mark Mascal and Cody Ross Pitts) delivered talks about their own research interests.
Jennifer Doudna’s work:
Doudna’s pioneering work in the development of CRISPR-Cas9 gene editing, in collaboration with Dr. Emmanuelle Charpentier, is widely regarded as one of the most significant discoveries in the history of science, and she was awarded the Nobel Prize in Chemistry in 2020. CRISPR-Cas9 gene editing is a biotechnology tool that allows scientists to make targeted changes to DNA. It uses a guide RNA to locate a specific DNA sequence, and the Cas9 enzyme acts like molecular scissors to cut the DNA at that spot. After the cut, the cell’s natural repair processes can introduce mutations or insert new genetic material.
Bacteria store DNA sequences of foreign pathogens, like viruses, in this “diary” after they have encountered them. These stored sequences are called spacers. Every time these bacteria survive an infection, they add a new entry (the DNA sequence of the virus) to their diary. When the bacteria encounter the same virus again, they can flip through their diary (CRISPR sequences) and find the exact DNA sequence they’ve seen before, helping them recognize the virus. This is where Cas9 comes into play to cut the DNA. After the cut, the cell’s repair system kicks in. It tries to fix the break, but it doesn’t always do so perfectly. This repair can have two possible outcomes. In non-homologous end joining (NHEJ), the cell “sticks” the broken ends back together but with errors, which can disable a gene (gene knockout). In homology-directed repair (HDR), if you provide a new DNA template, the cell can use it to repair the break more accurately, allowing you to insert or change genes.
CRISPR-Cas9 is widely used in research, medicine and agriculture due to its precision, efficiency and relative simplicity. CRISPR technology has been harnessed in the medical field, where novel therapies such as exagamglogene autotemcel (Exa-cel) have been developed to treat sickle cell disease and beta-thalassemia by editing patients’ stem cells to reactivate fetal hemoglobin production.
Moreover, in her talk, Doudna confirmed the partnership of UC Davis to join UC Berkeley and UC San Francisco in the Innovative Genomics Institute (IGI) to advance innovations in sustainable agriculture and climate change applications.
“One of the wonderful features of CRISPR is that it’s a technology that can be used on animals, plants, microbes — really any organism with DNA,” Doudna said. “I’m thrilled that we have now formally welcomed UC Davis as a full partner of the IGI, building on years of productive work together.”
Frances Arnold’s work:
Arnold started her conference talk by weaving together a story about what she considered to be her greatest achievement in her career: her cameo in the TV show “The Big Bang Theory.” Throughout her presentation, Arnold delved deep into the world of evolution, quoting Charles Darwin as one of her biggest inspirations to pursue her area of research: directed evolution. Darwin’s 1859 publication of “On the Origin of Species” was one of biology’s most landmark studies, as it introduced the idea of natural selection — natural processes and survival of the fittest determine the proportion of populations that will survive.
Arnold’s work on directed evolution focuses on artificial selection of enzymes, which are biological molecules who help speed up specific reactions. Although artificial selection has been applied into breeding animals, Arnold’s novel approach to applying this to enzymes allowed her and her team to allow enzymes to develop high specifications to perform functions in non-ideal environments.
Enzymes are made of chains of sub-molecules called amino acids. The sequence of amino acids in a cell can determine the structure and resultant function of the specific enzyme; even miniscule substitutions of one amino acid can have noticeable changes in the performance of the enzyme.
Arnold leveraged this power of mutations in order to kickstart the process of evolution. By evolving enzymes through subsequent generations, her work allowed for “enzymes to do the dirty work such as clean your laundry.”
“If you want something quite different from what you start with, then you have to iterate; […] you have to accumulate those mutations over multiple generations,” Arnold said.
Kendall N. Houk’s work:
Houk is a distinguished research professor of chemistry at UC Los Angeles, and her research focuses on computational organic chemistry, reaction mechanisms, pericyclic reactions and molecular design using quantum mechanical models. Computational chemistry uses simulations to model how atoms and molecules behave based on the rules of physics and quantum mechanics.
“It’s like Legos,” Dr. Dean Tantillo, a UC Davis organic chemistry professor and former Houk group member, said. “You are able to input the structure of molecules into powerful computers, which then calculate how electrons move, how bonds form or break and how the molecules change shape during reactions. These simulations can predict reaction pathways, energy changes and even whether a reaction is possible before anyone actually tries it in real life.”
Houk focused on a class of enzymes called pericyclases, which specialize in the processes of pericyclic reactions. Simply put, a pericyclic reaction is a type of chemical reaction where bonds are formed and broken at the same time in a circular flow of electrons, usually without needing outside help like heat or light.
To paraphrase Tantillo, bonds are made with pairs of electrons that interact within regions of space called orbitals. Orbitals can be imagined as cotton candy clouds, with each cloud representing an electron orbital around an atom. These clouds have nodes — like the parts where the cotton candy doesn’t really exist, kind of like a gap or a neutral zone. Each cotton candy cloud can have a flavor (positive or negative sign), representing the direction of the electron wave. If two clouds (orbitals) have the same flavor (meaning the same sign of the wave), their cotton candy can overlap — like two clouds of the same flavor mixing together to form a bigger, stronger cotton candy swirl. This overlap allows the electrons to flow smoothly from one atom to another, making bonds form and break in a coordinated, smooth manner.
However, if the clouds have different flavors (opposite signs), it’s like mixing two completely different cotton candy flavors. The clouds won’t mix well — they push against each other and the reaction won’t proceed as smoothly. In many pericyclic reactions, electrons from different parts of a molecule align in a circular or ring-like pattern, where the same-flavored clouds (orbitals with the same sign) overlap, allowing electrons to flow around the ring, making bonds form and break in one seamless motion.
Frontier Orbital Theory (FOT) is crucial to understanding pericyclic reactions because it explains why and how this smooth, concerted electron flow happens based on orbital interactions — specifically, the match between highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs). In Houk’s talk, he showed how enzymes called pericyclases take advantage of these orbital interactions to guide pericyclic reactions inside biological systems.
By using FOT, Houk’s group could predict how the cotton candy clouds (orbitals) of electrons in a molecule align and interact inside these enzymes, explaining why certain bonds form or break without the need for external heat or light. His computational simulations helped reveal that pericyclases create environments where primary and secondary orbital overlaps can result in one set of reactants ending up with multiple isomer (same formula, different orientations) products by entering a post-transition state bifurcation (PTSB), where one reactant can smoothly produce two products. Moreover, he shared various ongoing projects and collaborations with other laboratories regarding the use of pericyclic reactions for neurotherapeutics, enzyme-substrate interactions and pharmaceutical applications.
Elizabeth Neumann and Cici Zhai:
In addition to the numerous talks presented, the Miller Symposium serves as a platform to recognize outstanding students pursuing research in the department. Cici Zhai, a third-year cell biology major in Dr. Elizabeth Neumann’s lab, was a recipient of a $6,000 research grant to pursue research over the summer at UC Davis. Zhai’s project focused on a novel method to analyze the metabolic features of the spinal column while preserving its spatial integrity. Given the spinal column’s complexity, traditional techniques often struggle to maintain structural integrity during analysis.
Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), she and her team prepared fresh-frozen, unfixed and undecalcified rat spinal columns. To achieve high-resolution imaging (10 μm), they employed a tape-based sectioning approach, and Hematoxylin and Eosin staining confirmed the preservation of tissue architecture. Through this method, they were able to identify six distinct phospholipid profiles across spinal tissues, including the spinal cord, vertebrae, intervertebral discs, muscle and blood vessels. Her project’s findings demonstrate the potential of this technique for spatial biomolecular analysis while avoiding the degradation associated with bone decalcification.
“With the requirements of the grant, I have six uninterrupted weeks dedicated to research — an opportunity I wouldn’t normally have with my current schedule alongside my graduate student mentor,” Zhai said.
During the summer, Zhai also hopes to gain hands-on experience with our MALDI MSI TOF system and deepen her understanding of data analysis.
“Ultimately, I’d love to work toward publishing my own paper, though I know how much effort goes into that process,” Zhai said. “But for now, I’m excited to see where the research takes me.”
The Miller Symposium:
The Miller Symposium is more than just a platform for students to share their current work; it serves as a platform to meet, inspire or gain inspiration from a variety of individuals from diverse backgrounds.
“[The symposium] is a great opportunity to meet other scientists, trainees and talk about ideas that are coming out of convergence from all these minds gathered together in a beautiful place,” Doudna said.
Moreover, Arnold reflected on her past experience with pursuing research and reinforced that this platform serves to give students the courage to explore and challenge what may be known.
“I was there,” Arnold said. “We were all there. We were starting something that nobody had done before, so just do it. Learn as much as you can, because knowledge is like money in the bank.”
With the current situation in the scientific community regarding the loss of research funding and a complete shutdown of major research centers, the Miller Symposium serves as a way to continue pursuing research, providing students with valuable information and opportunities to hone their skills and grow their passion for the field.
The author would like to make the following acknowledgements for their contributions in writing this article:
Jennifer Doudna, Ph.D. (UC Berkeley)
Frances Arnold, Ph.D. (California Institute of Technology)
Kendall N. Houk, Ph.D. (UCLA)
Dean Tantillo, Ph.D. (UC Davis)
Cici Zhai (UC Davis)
Written by: Naren Krishna Jegan
