EicOsis LLC, a company founded by UC Davis distinguished professor Bruce Hammock to develop a non-opiate drug to relieve inflammatory pain in companion animals and target chronic neuropathic pain in humans and horses, can now add “Sacramento Region Innovator of the Year” to its list of accomplishments.
EicOsis won the award in the medical health/biopharmaceutical category of the annual Sacramento Region Innovation Awards Program. The program “recognizes the area's vibrant innovation community—from emerging to established companies—and their breakthrough creations,” according to sponsors Stoel Rives LLP, Moss Adams LLP and the Sacramento Business Journal.
“This project is an illustration of how fundamental science leads to real world applications, in this case addressing severe pain of humans and companion animals,” said Hammock, chief executive officer of EicOsis and a UC Davis faculty member who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “Our success in translation has been due largely to support from a number of institutes of the National Institutes of Health and a small team of hard-working scientists.”
The ceremony, honoring the winners of the eight categories, took place Nov. 7 in the Crest Theatre, Sacramento. Judges scored the finalists on novelty, market need, economic or social impact and disruption.
“It was an honor to be awarded the Sacramento Region Innovator of the Year in Medical Health and BioPharma,” said Cindy McReynolds, senior program manager of EicOsis and a UC Davis doctoral candidate studying pharmacology and toxicology. “The companies represented were inspiring, and it is great to be a part of the innovation going on in the Sacramento region.”
“Chronic pain is an enormous emotional and economic burden for more than 100 million people in the United States alone,” said Hammock, who co-founded EicOsis in December 2011 to alleviate pain in humans and companion animals. “The extreme and poorly treated pain that I observed as a medical officer working in a burn clinic in the Army, is a major driver for me to translate my research to help patients with severe pain.”
Phase 1 human clinical trials to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibitssEH, will begin Dec. 10 in Texas. The title: "A Single-Center, Double-Blind, Placebo-Controlled, Phase 1a Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sequential Dose Regiments of Oral EC5026 in Healthy Male and Female Subjects." Eight will participate; six with the drug candidate and two with the placebo. The technology was discovered in the Hammock lab and UC Davis has licensed patents exclusively to EicOsis.
“EC5026 is a key regulatory enzyme involved in the metabolism of membrane fatty acids,” Hammock said. "It's a novel, non-opioid and oral therapy for neuropathic and inflammatory pain. Inhibition of sEH treats pain by stabilizing natural analgesic and anti-inflammatory mediators."
The project is unique in that “there have been very few truly new types of analgesic compounds that have reached the market in the past 50 years,” Hammock said.
“The sEH enzyme is involved in regulating the activity of powerful anti-inflammatory fatty acids called EETs that are present in all cells in humans and animals,” the scientists explained in their awards application. “EETs are anti-inflammatory, analgesic, anti-hypertensive, but they are short lived molecules that are normally eliminated within seconds. By inhibiting sEH, EET levels can be increased by 4x or more and maintained at high anti-inflammatory and analgesic levels for 24 hours or longer.”
“The sEH inhibitors are very potent molecules that are designed for once daily oral dosing. They can also be administered intravenously for acute pain (e.g. equine laminitis),” they wrote. “Preclinical safety studies show that sEH inhibitors are very safe with no visible signs of toxicity at doses more than 100x higher than the therapeutic dose levels. Unlike conventional analgesics, they do not produce sedation or cognitive dysfunction and they have been shown to have no addiction liability, no adverse cardiovascular effects, and no adverse effects on the gastrointestinal tract. They can be safely co-administered with existing analgesic medications.”
Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Center for Disease Control and Prevention. The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims. Pain research is now one of the top priorities of the National Institutes of Health (NIH).
EicOsis advancement of EC5026 into clinical trials has been funded as part of the Blueprint Neurotherapeutics Network (BPN) of the NIH Blueprint for Neuroscience Research. The BPN is a collaboration of NIH Institutes and Centers that supports innovative research on the nervous system with the goal of developing new neurotherapeutic drugs.
EicOsis (pronounced eye-cosis), derives its name from eicosanoid, “the major backbone of chemical mediators in the arachidonate cascade,” said McReynolds. “It symbolizes the epoxide group in chemistry, which is key to the anti-inflammatory chemical mediators and where the biochemical target called soluble epoxide hydrolase works.”
The UC Davis Bohart Museum of Entomology will host an open house on “Arthropod Husbandry: Raising Insects for Research and Fun” from 1 to 4 p.m., Saturday, Nov. 16 in Room 1124 of the Academic Surge Building on Crocker Lane. The open house is free and family friendly.
"We will have a number of people who are expert at raising insects, both for research and for fun," said Tabatha Yang, Bohart Museum education and outreach coordinator. UC Davis student Andrew Goffinet, a former Bio Boot Camper, will be on hand to talk about rearing butterflies and moths. UC Davis entomology alumnus Lohit Garikipati will discuss praying mantids.
Another UC Davis entomology alumnus Nicole Tam will discuss rearing insects for research in the Geoffrey Attardo lab. Graduate student and Bohart associate Zaid Khouri will tell visitors how to rear tarantulas and millipedes for fun.
"We also will be discussing Madagascar hissing cockroaches as good options for 'starter pets' for kids, and some of the problems with stick insects (walking sticks)," she said. Visitors are invited to hold the hissers and stick insects and photograph them.
At 3 p.m., silkworm moth expert İsmail Şeker, a Turkish medical doctor who wrote a book about silkworm moths and the cottage silk industry in his home town, will show his newly produced video about the silkworm moth life cycle. Seker, also a talented videographer and a photographer, will answer questions following his 13-minute video presentation.
"This will be a fun open house for anyone considering a pet with an exoskeleton," Yang said."It will be good for educators to learn about classroom 'pets,' including those that do work with silk moths for life cycle lesson plans."
"Also, to kick off the holiday season we will have the unique wire jewelry by former entomology major Ann Kao, so people should be prepared to shop for some unique insect-inspired jewelry."
A family craft activity is also planned.
This is the last open house of the year. The next one will be on Jan. 18 when UC Davis graduate students from many different fields, "will be talking/displaying about their cutting edge research with insects," Yang said.
The Bohart Museum houses a global collection of nearly eight million specimens. It is also the home of the seventh largest insect collection in North America, and the California Insect Survey, a storehouse of the insect biodiversity. Noted entomologist Richard M. Bohart (1913-2007) founded the museum. It maintains a live "petting zoo," featuring Madagascar hissing cockroaches, walking sticks or stick insects, tarantulas, and praying mantids. The museum's gift shop, open year around, includes T-shirts, sweatshirts, books, jewelry, posters, insect-collecting equipment and insect-themed candy.
Director of the museum is Lynn Kimsey, professor of entomology at UC Davis. The staff includes Steve Heydon, senior museum scientist; Tabatha Yang, education and outreach coordinator; and Jeff Smith, who curates the Lepidoptera (butterflies and moths) section.
More information on the Bohart Museum is available on the website at http://bohart.ucdavis.edu or by contacting (530) 752-0493 or email@example.com.
“Many variables are known to affect the actual spray coverage in crop fields,” said Nansen, an associate professor in the UC Davis Department of Entomology and Nematology said. “These include tractor speed, spray nozzles, spray volume, boom height, adjuvants, and weather conditions. But which ones are the most important ones? And are there possible interactions among some of these variables?”
Through Smart Spray, an app designed for both iOS and Android phones, growers can optimize and perform quality control of pesticide spray applications in their strawberry fields, Nansen said.
Computer science major Krishna Chennapragada, now an alumnus, launched the programming and initial design, tallying some 500 hours before his graduation. Today's team, in addition to Nansen, is comprised of recruits Gabriel Del Villar, a 2019 computer science graduate, and Alexander Recalde, a senior majoring in computer science. Together they have amassed nearly 400 hours on the project.
“The project is truly multidisciplinary,” said Nansen, adding “One of the great things about UC Davis is that the barriers between colleges are very, very shallow.”
The Smart Spray app, they said, allows a user to predict spray coverage under different operational scenarios, including type of nozzles, spray volume, and tractor speed, as well as weather data, such as temperature, relative humidity and wind. A key part of the process: the user places a water-sensitive card in the field prior to a spray application, photographs it, and uploads it into the app.
“If you're a grower, you might expect that when you go out to spray, that the more that comes out of nozzle, the better coverage you'll get,” Nansen said. “But, for example, if the wind is too strong, the relative humanity is too low, the pressure is too high, or you're going too fast--even when you're spraying large volumes--you can get very poor coverage and it's costly. Excessive spray can also reach other fields or nearby urban developments due to so-called “spray drift”.”
“Typically, a grower will spray 100 to 150 gallons per acre when he or she sprays,” Nansen explained. The water-sensitive card is yellow, but it codes blue when it interacts with moisture. “These cards have been around a long time,” he said. “They cost about $1 a card, not cheap. But it's inexpensive when you're spending thousands of dollars to control the pests. And the pesticide companies can pay for the cards.”
“Say you want to predict your coverage before you spray tonight or tomorrow,” Nansen explained. “Look at the weather conditions; what is the forecast? Then how are you going to do this? What if you spray 100 gallons and want to go two miles per hour. You enter the data—and all the other applicable data--on the Smart Spray app. It will predict the coverage you'll get with nine different nozzles. Those are the nozzles the typical strawberry grower uses, a number we based on almost 3000 experimental sprays over three years. So we did a lot of homework on this, for example—different spray rigs, different sizes of crops, different spacing of plants, and under different weather conditions. We covered all the ranges we could think of. We collected the water and operational data and we did the progression analysis (for the modeling).”
“Using this prediction, you can give it a name, say Field 6, and access it from the database,” Nansen said. “It's about quality control. It's a tool to predict and do quality control. It empowers the grower and also the sprayer to do a better job. For example, if the conditions are bad and the app shows the spraying will be only 20 percent effective, you shouldn't be spraying.”
“The Smart Spray is not just insecticides--it's fungicides, herbicides, and whatever you want to spray,” Nansen noted. “This app was developed for strawberries; if it were used for soybeans, onions and cabbage, it would still be useful but the accuracy would be off.” Pending apps: almond, pistachio and tomato.
The computer scientists enjoy working on the project. Recalde attended a Central Coast sprayers' meeting to talk about the app. “I heard ‘Oh, wow, you look so young!' he remembered. “Then we told them about this useful tool, different ways that technology can be applied to agriculture. They were really interested in how technology can improve what they're doing.”
Del Villar, whose computer interests also include teaching youth how to code, said he eagerly looks forward to making the Smart Spray app even better and more useful. Fluent in Spanish, as well as English, he plans to translate the app into Spanish. Other language translations are also in the works.
Now the team is seeking feedback to improve the app. “We're hoping growers will embrace it,” Nansen said, “and help us find ways to improve it.”
One feedback from Eric Flora, global field development and manager of Crop Enhancement, Inc., Paso Robles: “I think Smart Spray is a very helpful tool for growers and advisers as a guide to select spray tips, spray volumes, tractor speed, and other important factors to maximize sprayer coverage. Using spray cards is the best and simplest way to know, if you are penetrating everywhere in the canopy your pest target is a problem--placing cards where the specific pests attack the host gives the best information.”
State, federal and industry grants, including the California Strawberry Commission and the Floriculture and Nursery Research Initiative (FNRI) of the U.S. Department of Agriculture's Agricultural Research Service, help fund the project.
California grows about 88 percent of the nation's strawberries on approximately 34,000 acres along the California coast, according to the Strawberry Commission. Strawberries are available year-around in California.
Statewide, fresh strawberry production averages 50,000 pounds per acre each season. The approximately 300 strawberry growers hail from five distinct areas of California: Watsonville/Salinas, Santa Maria, Oxnard, Orange County/San Diego, and the Central Valley. They include multi-generation farming families growing both organic and conventional strawberries.
For more information on the Smart Spray app, access the manual at https://bit.ly/2q3lsL3 or contact Nansen at firstname.lastname@example.org or 530-752-2728.
Research Highlight Editor Lysa Maron spotlighted the work in her article, “Breaking or Sneaking into the Fortress: the Root Endodermis is a Defence Wall Against Nematode Infection.” The journal also showcased the research team's image of a nematode on the cover.
Siddique led the 10-member international research team in discovering the role of a plant's endodermal barrier system in defending against plant-parasitic nematodes. The Plant Journal published the research, “Root Endodermal Barrier System Contributes to Defence against Plant‐Parasitic Cyst and Root-Knot Nematodes, in its July 19 edition.
“We discovered that the integrity of the endodermis—a specialized cell layer that surrounds the vascular system and helps regulate the flow of water, ions and minerals--is important to restrict nematode infection,” said Siddique, an assistant professor in the UC Davis Department of Nematology who joined the faculty in March after serving several years at the University of Bonn.
“We found that having defects in endodermis make it easier for parasites to reach the vascular cylinder and establish their feeding site. Although, this finding is a result of basic research, it opens new avenues to for breeding resistance against cyst nematodes in crops.”
Maron noted that “Roots are a truly amazing plant structure: they conquer the underground, form complex structures that anchor the plant, let water and nutrients in, but must not dry out. Roots store energy, send signals to the aboveground parts of the plant and to neighbors, and defend the plant against soil-borne pathogens. Within the root, the endodermis is the barrier that separates the inner vasculature from the outer cortex. If the root is a fortress, the endodermis is the gated wall. Cell wall reinforcements such as the casparian strip (CS), lignin deposition, and suberin seal the apoplast of the endodermis throughout different parts of the root. These reinforcements allow the diffusion of water and nutrients to and from the vascular tissue while blocking its penetration by pathogens such as bacteria and fungi (Enstone et al., 2002).”
“But roots also face pathogens of a different kind: root-infecting, sedentary endoparasites such as cyst nematodes (CNs) and root-knot nematodes (RKNs),” Maron wrote. “These pathogens infect a variety of important crops and cause significant yield losses (Savary et al., 2019).”
Maron quoted Siddique: “According to Siddique, investigating root traits that affect plant-nematode interactions is important for finding new strategies for plant protection. Screening for natural variation in suberin- and lignin-related traits might help identify and develop stronger fortresses, i.e., plants with enhanced resilience against pathogens, drought, and nutrient deficiency.”
Siddique collaborated with scientists from Germany, Switzerland and Poland: Julia Holbein, Rochus Franke, Lukas Schreiber and Florian M. W. Grundler of the University of Bonn; Peter Marhavy, Satosha Fujita, and Niko Geldner of the University of Lasuanne, Switzerland; and Miroslawa Górecka and Miroslaw Sobeczak of the Warsaw University of Life Sciences, Poland.
“Plant-parasitic nematodes are among the most destructive plant pathogens, causing agricultural losses amounting to $80 billion annually in the United States,” said Siddique in an earlier news story. “They invade the roots of almond, tomato, beets, potato or soybeans and migrate through different tissues to reach the central part—the vascular cylinder--of the root where they induce permanent feeding sites.”
“These feeding sites are full of sugars and amino acids and provide the parasite all the nutrients they need,” Siddique explained. “A specialized cell layer called the endodermis surrounds the vascular system and helps regulates the flow of water, ions and minerals into and out of it. However, the role of endodermis in protecting the vascular system against invaders such as nematodes had remained unknown.”
The research was funded by a grant from the German Research Foundation.
The class, set from 8:45 a.m. to 5 p.m., Saturday, Dec. 7 in the Harry H. Laidlaw Jr. Honey Bee Research Center on Bee Biology Road, will be taught by Extension apicuturist Elina Niño of the UC Davis Department of Entomology and Nematology faculty and director of the California Master Beekeeper Program, and lab assistants Robin Lowery and Nissa Svetlana Coit.
“Robin and Nissa will be leading us through the practical part of the wax working day,” announced Wendy Mather, program manager of the California Master Beekeepers Program. “This class is perfect for the hobby and sideline beekeeper and for other individuals interested in learning the basics of working with wax.”
The instructors said the class "will be a creative and science-based class learning the what, why and how of beeswax, making candles, lotion bars, beeswax food wraps, lip balm and dipped flowers to take home.” The products are wonderful for holiday gifting, they said.
As a bonus, the instructors will provide an overview of the honey extraction process, and learn bottling, labeling rules and regulations, and how to perform a honey tasting.
Class participants will have an opportunity to make candles with wicks, use molds, pour wax into jars or cans, dip flowers in wax, and make hand lotion, chapsticks, and wax reusable food wraps.
The two lab assistants are daily exposed to bees, beekeeping, and all things related to honey bee husbandry, said Mather. Lowery, a two-year beekeeper, assists with managing the apiary and the research at the E. L. Nino lab. "She has been making gifts for special occasions for over 15 years and looks forward to modeling how to dip and roll candles, make sealing wax, lotion and lip balm, and wax food wrappers," Mather said.
Beeswax is a natural wax produced by worker honey bees, which have eight wax-producing glands in the abdominal segments. Hive workers collect the wax and use it to form cells for honey storage and for larval and pupal protection. When beekeepers extract the honey, they remove the wax caps from the honeycomb frame with an uncapping knife or machine.
Beewax has long been used for making candles (they are cleaner, brighter and burn longer than other candles) and for cosmetics and encaustic paintings. Wax food wrappers, used to wrap sandwiches and cover bowls of food, are environmentally friendly, sustainable, economical, and a reusable alternative to plastic bags. Statistics show that globally, people use an estimated one trillion single-use bags every year, or nearly 2 million a minute. While beeswax is a natural wax, plastic bags and plastic bags contain chemicals, and there is concern that chemicals can leach into the food.
The $235 registration fee covers a continental breakfast, snacks, lunch and refreshments, and materials. Participants make and take two of each item. The registration deadline is Nov. 23, said Mather, who may be reached at email@example.com for more information. To register, access https://registration.ucdavis.edu/Item/Details/589.