Trace detection of such organophosphates as triazophos, parathion, and chlorpyrifos is “extremely important for various reasons, including food safety, environmental monitoring, and national health,” a team of scientists, including UC Davis distinguished professor Bruce Hammock pointed out last week, in announcing that their scientific paper has just been named the “Extramural Paper of the Month” by the National Institute of Environmental Health Sciences (NIEHS).

The research involves the development of a DNA-based sensor amplification system demonstrated in a fluorescence immunoassay that can detect, both simply and rapidly, trace amounts of organophosphate pesticides (OPs) in food products.

The paper, “Competitive Fluorescent Immunosensor Based on Catalytic Hairpin Self-Assembly for Multiresidue Detection of Organophosphate Pesticides in Agricultural Products,” appeared in the February edition of the Food Chemistry journal and is republished in June as “Paper of the Month."

Maojun Jin, who served a year (September 2019 to September 2020) as a visiting scholar in the Hammock laboratory, UC Davis Department of Entomology and Nematology, led the research team, and is the senior author and corresponding author. He is now a professor in the Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences. His doctoral student, Yuanshang Wang, is the first author.

“I'm very proud of what Maoiun and his team have accomplished,” said Hammock, who directs the NIEHS-UC Davis Superfund Research Program.  The research was partially funded by his Superfund grant, and his NIEHS RIVER (Revolutionizing Innovative, Visionary Environmental Health Research) Award. 

In addition, the research drew financial support from the National Natural Science Foundation of China, Central Public-interest Scientific Institution Basal Research Fund, and the Central Public Interest Scientific Institution Basal Research Fund for the Chinese Academy of Agricultural Sciences.

(See full story on the UC Davis Department of Entomology and Nematology website. No images can currently be loaded on the Bug Squad blog due to server issues.)

Today being April 20 and a worldwide focus on cannabis, it seems appropriate to mention a research poster on "A Nanobody-Based Immunoassay for Detecting Moldy Marijuana" that won the top undergraduate poster at the 23rd annual R. Bryan Miller Symposium.

Congrats to UC Davis undergraduate entomology major Rachel Shey, a research assistant in the laboratory of UC Davis Distinguished Professor Bruce Hammock, who won not only the poster competition, but more importantly, the $5000 Francesca Miller Undergraduate Research Award that will fund six weeks of full-time summer research.

Well done, Rachel!

The symposium, sponsored by the Department of Chemistry and recently held in the UC Davis Conference Center, featured cutting-edge research in chemical biology, organic, and pharmaceutical chemistry. It memorializes Professor Miller (1940-1998) the 1985-90 chair of the Department of Chemistry and the 1997-1998 chair of the Academic Senate. 

“We're very proud of Rachel,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.  “Rachel winning the undergraduate research award as well as the first-place award for her poster on her research—that's no surprise.  She is enthusiastic about science and has wonderful collaborations with our scientists.   She is one of those rare people who can cross disciplines, and in this case, integrate molecular biology, chemistry, and analytical chemistry to address a serious problem in the world food supply.  Not only that, but she makes the lab had more fun place to be.” 

In her abstract, co-authored with mentor Hammock and project scientist Mark McCoy of the Hammock lab, Shey wrote:

“Have you ever forgotten about a bagel on the counter and come back a few days later to find that it has grown a thin layer of fuzzy green mold? Most people know not to eat it, but why not? Aspergillus fungus produces a toxin called aflatoxin, which is the reason moldy bread, bitter peanuts and other foods may not be safe to eat. Aspergillus grows on virtually all major crops in the world, and aflatoxin is present wherever Aspergillus grows.”

“I am developing a nanobody-based immunoassay for the detection of aflatoxin B1 in the matrix of hemp bud, intended to simulate cannabis.  Nanobodies, also known as VHHs (heavy chains) represent a new technology.  They are small antibodies which are derived from camelids and sharks. Unlike regular antibodies, nanobodies are made of only heavy chains and are therefore about ten times smaller than traditional monoclonal antibodies or polyclonal antibodies. Because nanobodies are encoded on a single polypeptide chain, they can be grown in E. coli cheaply and in large amounts.” 

Shey related that “the first step is to optimize the concentrations of the substrate, coating antigen, and nanobody for the assay; once this is done, we can assay extracts of hemp bud samples.  These samples tend to contain other reactive molecules that can create unusual signals by binding to nanobodies undesirably. This is known as the “matrix effect” and must also be controlled for, either by further diluting the sample, while paying close attention to the limit of detection, or processing the samples in a different way to reduce the amount of potential interference.”

 “Cannabis is highly regulated in California,” Shey pointed out, “but batches of cannabis that fail testing are usually sold on the black market rather than at a regulated dispensary.  Consumers who decide to run the risk of purchasing cannabis from an unregulated seller would also benefit from immunoassays for monitoring the levels of various pesticides and known contaminants, including aflatoxin.  This immunoassay could be useful for not only commercial labs analyzing cannabis, but also consumers purchasing cannabis illegally.” 

Shey also presented her poster research at two other UC Davis conferences this year: the Undergraduate Research, Scholarship and Creative Activities Conference (URSCA) and the 2023 Richard LaRock Conference. 

Rachel, from Walnut Creek, and home-schooled from K-12 in the RAN Academy (RAN is an acronym for Rachel and her brothers Aaron and Nicholas), received her high school diploma in 2020. She enrolled at UC Davis in September 2020 and joined the Hammock lab in March 2022. 

“I was really drawn to entomology because I've loved playing with insects ever since I was a kid,” Rachel said. “When I took organic chemistry, I fell in love with the unique style of problem solving and I grew passionate about its practical aspects as well.” 

In the Hammock lab, she helps in immunoassay experiments, delivers presentations to the lab, and learns about research and science. “I am developing proficiency with ELISA (enzyme linked immunosorbent assay) and phage work,” Shey said. She is working on an independent project funded by an Innovation Institute for Food and Health Undergraduate Research Fellowship (IIFL) from the UC Davis Undergraduate Research Center. It involves the detection of aflatoxin in mouse brain tissue. 

Shey also is a research assistant (since November 2022) in the lab of Cody Ross Pitt, assistant professor, UC Davis Department of Chemistry, where she is learning organic synthesis methods, including setting up air-sensitive reactions, working up reactions, using columns to purify the crude material, and operating a rotary evaporator (rotovap). 

She has served a general and organic chemistry tutor or the UC Davis Academic Assistance and Tutoring Center (AATC) since September 2021. She staffs the drop-in area in the library and the online Zoom drop-in room for several hours each week. “I assist students with chemistry questions with the goal of helping my students develop study skills.” 

Shey also worked part-time for almost two years as a city news reporter for the California Aggie, the UC Davis student-run newspaper.

Her career plans: to study organic chemistry and obtain a doctorate in chemistry. “I would love to work in medicinal chemistry or agrochemistry.”

“When I first talked to her she was excited over epoxides as such interesting chemical functionalities,” said Hammock, known for his expertise in chemistry, toxicology, biochemistry and entomology. Early in his career, he founded the field of environmental immunoassay, using antibodies and biosensors to monitor food and environmental safety, and human exposure to pesticides. His groundbreaking research in insect physiology, toxicology led to his development of the first recombinant virus for insect control.

“I saw Barry Sharpless last week, who like Linus Pauling, won two Nobel Prizes," Hammock said.   She reminds me of Barry. The world needs more undergrads like Rachel.” 

Congrats to UC Davis distinguished professor Walter Soares Leal of the Department of Molecular and Cellular Biology, and a former chair of the Department of Entomology, on his induction as a Fellow of the National Academy of Inventors (NAI).

Leal, a leading global scientist and inventor in the field of insect olfaction and communication and known for his impact in the fields of molecular, cellular biology and enotmology, received his medal at a June ceremony in Phoenix.

NIA selected him an NAI Fellow in 2019. However, the COVID pandemic cancelled the 2019 ceremony in Phoenix. Then in 2020,  travel restrictions interfered with his plans to attend the Tampa, Fla., ceremony. Elected Fellows are required to attend the induction ceremony within two years of election in order to receive their award.

Leal attended the ceremony with his wife, Beatriz;  daughter Helena; and son Gabriel. Both have co-authored papers in the Leal lab, "so they represent all visiting scholars, collaborators, postdocs, project scientists, graduate students, and undergraduate students in my lab," he commented.  (See video of the awarding of the medals)

NAI singles out outstanding inventors for their “highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development, and welfare of society.” Election to NAI Fellow is the highest professional distinction accorded solely to academic inventors. The NAI Fellow program has 1,403 Fellows worldwide representing more than 250 prestigious universities and governmental and non-profit research institutes.

UC Davis chancellor emerita Linda Katehi, an NAI fellow inducted in 2012, nominated Leal for the honor for his “novel, sustainable and continued contributions to the field of entomology and for their greater implications in molecular and cellular biology and the understanding of disease and prevention.”   At the time, Leal held 28 Japanese and two U.S. patents.

Leal is the second faculty member affiliated with the Department of Entomology and Nematology to be selected an NAI fellow. Distinguished professor Bruce Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, received the honor in 2014.  

Leal, an expert in insect communication investigates how insects detect odors, connect and communicate within their species; and detect host and non-host plant matter. His research, spanning three decades, targets insects that carry mosquito-borne diseases as well as agricultural pests that damage and destroy crops. He and his lab drew international attention with their discovery of the mode of action of DEET, the gold standard of insect repellents. 

He and his collaborators, including Nobel Laureate Kurth Wuthrich (Chemistry 2002), unravel how pheromones are carried by pheromone-binding proteins, precisely delivered to odorant receptors, and finally activated by pheromone-degrading enzymes.

That led to Leal's identification of the sex pheromones of the navel orangeworm (Amyelois transitella), a pest of almonds, figs, pomegranates and walnuts, the major hosts. This has led to practical applications of pest management techniques in the fields.

At the time of his election to NAI Fellow, Joe Rominiecki, communications manager of Entomological Society of America (ESA), said Leal has “greatly advanced scientific understanding of insect olfaction. He has identified and synthesized several insect pheromones, and his collaborative efforts led to the first structure of an insect pheromone-binding protein."

ICE Council. Leal was recently elected chair of the International Congress of Entomology Council, which selects a country to host the congress every four years and which supports the continuity of the international congresses of entomology. Leal succeeds prominent entomologist May Berenbaum of the University of Illinois, Urbana-Champaign, editor-in-chief of the journal, Proceedings of the National Academy of Sciences and a 2014 recipient of the National Medal of Science. 

“I have big shoes to fill,” he said. 

Leal's name is currently on the ESA ballot to become an Honorary Member, the highest ESA honor.  The Royal Entomological Society named him an Honorary Fellow in 2015. 

A native of Brazil, educated in Brazil and Japan, and fluent in Portuguese, Japanese and English, Leal received his master's degree and doctorate in Japan: his master's degree at Mie University in 1987, and his doctorate in applied biochemistry at Tsukuba University in 1990. Leal then conducted research for 10 years at Japan's National Institute of Sericultural and Entomological Science and the Japan Science and Technology Agency before joining the faculty of the UC Davis Department of Entomology in 2000. He chaired the department from July 2006 to February 2008.

Leal co-chaired the 2016 International Congress of Entomology meeting, "Entomology Without Borders," in Orlando, Fla., that drew the largest delegation of scientists and experts in the history of the discipline: 6682 attendees from 102 countries. 

Among his many other honors, Leal is a Fellow of ESA, the American Association for the Advancement of Sciences and the California Academy of Sciences. He is a past president of the International Society of Chemical Ecology and corresponding member of the Brazilian Academy of Sciences.  In 2019, ESA selected him to present its annual Founders' Memorial Lecture, the first UC Davis scientist selected to do so.

This year Leal received the UC Davis Academic Senate's Distinguished Scholarly Public Service Award for his series of four global webinars educating the public about COVID-19. The online symposiums drew more than 6000 viewers from 35 countries. Hammock, who nominated Leal for the award, praised his “extraordinary spirit of public service and selflessness in creating, organizing, and moderating a series of four COVID-19 symposiums at the beginning of the COVID-19 pandemic. He spearheaded public awareness, helped educate the public, eased concerns, and translated the scientific data into lay language. His symposiums drew global attention and brought prestige to UC Davis. It was a crucial time in our history.”

In addition to research and public service, teaching is another of Leal's passions. The UC Davis Academic Senate selected him for its 2020 Distinguished Teaching Award for Undergraduate Teaching,  and the College of Biological Sciences singled him out for its 2022 Faculty Teaching Award.

"I don't teach because I have to," Leal recently said. "I teach because it is a joy to light the way and to spark the fire of knowledge."

While in the U.S. Army, UC Davis distinguished professor Bruce Hammock worked as medical officer in a burn clinic.  His mother served 15 years as a nurse in a children's hospital burn center.

Hammock, who now holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, knows too well what fire can do to victims.

So do other members of the Hammock lab and the Department of Surgery, University of Cincinnati College of Medicine (UC CoM).

They've just published research in the Proceedings of the Natural Academy of Sciences detailing their discovery of a key regulatory mechanism in inflammation that may lead to resolving inflammation in burn patients, as well as sepsis, cancer and COVID patients.

Basically, they discovered a pathway that regulates the immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.

“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author and researcher Cindy McReynolds of the Hammock lab and director of research at EicOsis, a Davis-based company founded by Hammock. Hammock, the corresponding author of the publication, has been involved in enzyme research for more than 50 years.

The eight-member team, using a rodent model, found that the metabolites of linoleic acid formed by the enzyme, soluble epoxide hydrolase (sEH), drive deleterious inflammation after injury. These metabolites, known as lipid mediators, regulate inflammation, blood pressure and pain. Drugs that inhibit the sEH enzyme and resolve inflammation could lead to a better patient outcome. 

“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.”  

“The immunological disbalance we see in many cases of severe burn injury, trauma and sepsis pose a huge clinical challenge as we lack the understanding of how to diagnose and treat it,” said co-lead author Dr. Christian Bergmann, formerly with UC CoM's Department of Surgery and now headquartered in Germany with the University of Ulm's Department of Trauma Surgery, Hand, Plastic and Reconstructive Surgery. “With this work, we reveal an important mechanism how immune cells are functionally disabled by sEH-derived metabolites of linoleic acid.” 

 The research, titled "sEH-Derived Metabolites of Linoleic Acid Drive Pathologic Inflammation while Impairing Key Innate Immune Cell Function in Burn Injury,” is co-authored by Debin Wan, formerly of the Hammock lab and now a scientist at Escape Bio, San Francisco; Nalin Singh of the Hammock lab; and three UC CoM researchers: Charles Caldwell, professor and director, Division of Research, Department of Surgery; Dorothy Supp, adjunct professor in the Department of Surgery and a scientific staff member at Shriners Children's Ohio; and Holly Goetzman, principal research assistant in the Caldwell lab.

It's a complicated research project, but a crucial one to help humanity.

And that's what EicOsis is all about, as well.  Hammock founded EicOsis in December 2011 to advance novel, safe and effective oral treatments for patients suffering from pain and inflammation. The LLC is developing a new class of oral non-narcotic analgesics based on inhibition of the soluble epoxide hydrolase enzyme. Human clinical trials are underway to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibits sEH. The sEH inhibitors have already shown to be effective for inflammatory and neuropathic pain in animals, with no apparent adverse or addictive reactions.