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(SD2022-133) Methods to monitor guanitoxin cyanobacterial blooms

Freshwater is essential for drinking and agriculture, yet potable watersheds are increasingly impacted by the undesirable high-density growth of algae and/or cyanobacteria. Understanding, monitoring, and remediating harmful algal/cyanobacterial blooms (HABs/cyanoHABs) and their associated toxins are essential to reducing their societal impact. Recent scientific and technological advances continue to improve environmental cyanoHAB detection and prediction;  however, the vast cyanotoxin structural chemodiversity creates challenges in their comprehensive detection and quantification using standard analytical chemistry assays. In contrast, quantitative molecular biological detection of biosynthetic genes via PCR provides a multiplexable and cost-effective monitoring strategy to identify the toxic potential of blooms independent of active toxin synthesis. The biosynthetic gene clusters (BGCs) for important freshwater cyanotoxins like microcystin, cylindrospermopsin,  saxitoxin,  and anatoxin-a have been defined and applied toward detection over the past decades. However, the biosynthetic pathway and genes for guanitoxin, the only known natural organophosphate neurotoxin, have yet to be described.Previously known as anatoxin-a(s),  guanitoxin is an irreversible inhibitor of acetylcholinesterase, sharing an identical mechanism of action with organophosphates like the synthetic chemical warfare agent sarin and the banned pesticide parathion. Guanitoxin induces acute neurological toxicity that can lead to rapid death, showing comparable lethality (LD50 = 20 μg/kg i.p.) to saxitoxin, the most potent known cyanotoxin. Sporadic detection in the Americas, Europe, and Middle East coupled with bloom-related animal deaths consistent with guanitoxin exposure suggests that this toxin could be an under-recognized threat in global watersheds. 

Novel Genetic Switch for Inducing Gene Expression

Prof. Sean Cutler and colleagues at the University of California, Riverside have engineered a system and methods to induce gene expression in plants and organisms, including mammals, using the chemical compound mandipropamid. Using the PYR/PYL/HAB1 promoter system, the PYR1/HAB1 system is reprogrammed to be activiated with mandipropamid.  When the PYR1/HAB1 system dimerizes through chemical induced dimerization (CID) with mandipropamid, the system functions as a control switch for gene expression. This technology has been demonstrated to advantageously accelerate citrus breeding.  It may be applied to improve CAR T-cell therapy and agricultural crops. Fig 1: UCR’s PYR1/HAB1 system is programmed through chemical induced dimerization (CID) initiated by mandipropamid to function as a switch for agrochemical control of gene expression.  

Vascular Anastomosis Device

Researchers at the University of California, Davis have developed a surgical device to facilitate vascular anastomosis procedures with enhanced ease and speed.

Deep Learning-Based Approach to Accelerate T cell Receptor Design

Researchers at the University of California, Davis have developed a deep learning simulation model to predict mutated T-cell receptor affinity and avidity for immunotherapy applications.

High Accuracy Machine Learning Model for Predicting Liver Cancer Risk

Researchers at the University of California, Davis have developed a method to predict if patients diagnosed with nonalcoholic fatty liver disease are at risk for developing liver cancer using a machine learning algorithm that analyzes a variety of easily available phenotypes and risk factors.

Positive Allosteric Modulators Target TRPV1 with Analgesic Effects

Researchers at the University of California, Davis have developed de novo positive allosteric modulators (PAMs) that bind to TRPV1 proteins involved with pain-sensing in order to provide analgesic effects.

Reinforcement Learning with Real-time Docking of 3D Structures for SARS-COV-2

The inventors propose a novel framework generating new molecules that potentially inhibit the Mpro protein, the main protease of SARS-COV-2. The technology combines deep reinforcement learning (RL) with real-time molecular docking on the 3d structure of Mpro using AutoDock Vina, an open-source program for doing molecular docking. A second second docking software, Glide, was used to validate the generated molecules. The AutoDock and Glide docking softwares showed consensus on 41 molecules as potential potent Mpro inhibitors that were sufficiently easy to synthesize. The inventors show that this method samples the drug chemical space efficiently, covering a much broader space than molecules submitted to the COVID moonshot project, and the molecules have the correct shape and non-bonded interactions to fit into the binding pocket. Moreover, this approach only relies on the structure of the target protein, which means it can be easily adapted for future development of other inhibitors.

Synthetic Biology Methods and Systems to Synthesize Strigolactone

Prof. Yanran Li and colleagues from the University of California, Riverside have developed a biosynthetic method for producing different strigolactones by designing different biosynthetic pathways in engineered microbial systems. The invention includes engineered E. coli - S. cerevisiae co-culture systems for the biosynthesis of both non-canonical and canonical SLs, including but not limited to carlactone (CL), carlactonic acid (CLA), 5-deoxystrigol(5DS), 4-Deoxyorobanchol (4DO) and orobanchol. This technology allows SLs to be biosynthetically produced in large scale for use in innovative  agrochemicals such as phyto-regulators,  fertilizers, biostimulants that enhance the nutrient uptake efficiency. Fig 1: Mimicking plant strigolactone pathway distribution in the engineered E. coli-S. cerevisiae coculture.

Inter-Brain Measurements for Matching Applications

This technology utilizes inter-subject measurement of brain activity for the purpose of matching individuals. In particular, the invention measures the similarity and differences in neural activity patterns between interacting individuals (either in person or online) as a signature measurement for their matching capabilities. Relevant applications can be in the world of human resources (e.g., building collaborative teams), patient-therapist matching and others. The application relies on the utilization of both custom and commercial devices for measuring brain activity.

Aluminum Microchips for Biosensing and Pathogen Identification

Prof. Quan Cheng and colleagues from the University of California, Riverside have developed aluminum (Al) microchips for highly sensitive SPR detection of bioanalytical targets. This technology allows for determination of binding kinetics of drug targets and disease marker detection. In addition to applications for SPR, these Al microchips enable other surface-based techniques such as enhanced Raman spectroscopy and MALDI-MS for direct pathogen identification. Compared to traditional gold substrates, Al has a broad range of advantages. It is more plasmonically active, leading to high optical sensitivity, and it is chemically flexible for design of various analytical platforms. Al also has several manufacturing benefits that make it commercially appealing when compared to gold, such as higher abundance, lower cost, and simple integration into existing manufacturing processes such as CMOS. Fig 1: (Top) Fabrication of aluminum microchips. (Bottom) Aluminum demonstrates a high theoretical and practical plasmonic activity correlating to a higher detection sensitivity for biological targets.  

Plasmonic Gold Microchips for Swift Microbial Identification with MALDI-MS

Prof. Quan Cheng and colleagues from the University of California, Riverside have developed a gold microchip consisting of a nanoscale film fabricated on a gold substrate for highly effective, matrix-free laser desorption ionization mass spectrometry (LDI-MS) analysis of lipids. This technology allows for effective analysis of low mass metabolites without the need for time consuming extraction methods. The microchip also enhances fluorescent signal through metal enhanced fluorescence (MEF) allowing single cells to be located easily and improves ionization of lipids. Fig 1: Gold microchips enable localization of cells with MEF and efficient ionization of lipid species. The lipid fingerprint can then be used to trace changes caused by toxicants or identify microbial species present.  

One-Pot Multienzyme Synthesis of Sialidase Reagents, Probes and Inhibitors

Researchers at the University of California, Davis, have developed an environmentally friendly one-pot multienzyme (OPME) method for synthesizing sialidase reagents, probes, and inhibitors.

DNA-based, Read-Only Memory (ROM) for Data Storage Applications

Researchers at the University of California, Davis have collaborated with colleagues at the University of Washington and Emory University to develop a DNA-based, memory and data storage technology that integrates seamlessly with semiconductor-based technologies and conventional electronic devices.

Nanopore Sensor to Characterize Nano and Microscale Particles and Cells

Researchers at the University of California, Riverside can discriminate between mixed populations of cells and particles in solution using pressure to displace objects across a nanopore multiple times.  Ionic current flow through the nanopore indicates the pressure required to translocate the object in the pore, which correlates to the object’s mass and volume.  Key to these results is that a nanopore sensor allows pressure oscillations to capture and release repeatedly the same object to learn about its inertia and morphology.  Such data can provide details about the size and shape of analytes, their morphologies and structural constraints, or even pathological conditions of living cells. Fig. 1 Nanopore sensing of differently sized cells in a mixed bacterial culture.  

Protein Inhibitor of Type II-A CRISPR-Cas System

The inventors have discovered three protein inhibitors of the type II-A CRISPR-Cas system that specifically inhibit Cas9 from staphylococcus aureus. This finding is of potential importance to many companies in the CRISPR space. 

Using Vacuolar Na+/H+ Antiporters to Increase Salt Tolerance in Plants

Researchers at the University of California, Davis have developed a method that increases salt tolerance in plants. This method introduces a polynucleotide that encodes a Na+/H+ transporter polypeptide.

Expressing Multiple Genes From A Single Transcript In Algae And Plants

Green algae have been promoted as vehicles for the production of biofuels, pharmaceuticals, food additives, vaccines, and for toxic substance remediation, and many plants are the focus of efforts to produce drought tolerant, pest resistant, or more nutritious crops. Many of these engineering efforts rely on expression of multiple transgenes (e.g. in a multistep metabolic pathway to avoid accumulation of a toxic intermediate). It can also be useful to produce two or more proteins in a particular stoichiometry, as in a heterodimer that requires equimolar production of two polypeptides. Whether the goal is to express one transgene, or several, most efforts to transform plants and algae require cotransformation of the gene of interest with a selectable marker, such as a gene that confers resistance to a drug or herbicide, or complements an auxotrophy. Unfortunately, commonly used methods for co-transformation of algae and other plants are very inefficient. UC Berkeley investigators have developed a method for polycistronic gene expression,  and show how to achieve this using the organism's own sequences, without recourse to viral elements or other foreign elements, which is important for any technology where bioproducts are generated, since these may be used on humans (cosmetics) or in humans (food additives), especially crop technology.

A Fully Integrated Stretchable Sensor Arrays for Wearable Sign Language Translation To Voice

UCLA researchers in the Department of Bioengineering have developed a novel machine learning assisted wearable sensor system for the direct translation of sign language into voice with high performance.

Composition and Methods of a Nuclease Chain Reaction for Nucleic Acid Detection

This invention leverages the nuclease activity of CRISPR proteins for the direct, sensitive detection of specific nucleic acid sequences. This all-in-one detection modality includes an internal Nuclease Chain Reaction (NCR), which possesses an amplifying, feed-forward loop to generate an exponential signal upon detection of a target nucleic acid.Cas13 or Cas12 enzymes can be programmed with a guide RNA that recognizes a desired target sequence, activating a non-specific RNase or DNase activity. This can be used to release a detectable label. On its own, this approach is inherently limited in sensitivity and current methods require an amplification of genetic material before CRISPR-base detection. 

A novel method for increasing MHC presentation of oncogene derived neoantigens

The invention describes a platform technology that increases MHC presentation of oncogene derived peptide neoantigens that do not normally occur in the cell. The platform has already been used to identify a method of increasing KRAS G12 D/V derived peptide presentation on MHC- I.

Monoclonal Antibodies Specific to Canine PD-1 and PD-L1

Researchers at the University of California, Davis have developed monoclonal antibodies with multiple applications relevant to canine PD-1 and PD-L1.

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