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. 

Prof. Min Xue from the University of California, Riverside and Prof. Wei Wei from the Institute for Systems Biology have developed materials and  methods to detect and measure FA uptake alone or simultaneously with protein detection in multiplex down to single-cell resolution. FA analogs with an azide functional group mimics natural FAs. Specially designed small polymers are used to efficiently assay the FA analogs and produce fluorescent or chemical signals upon binding. The technology is compatible with protein analysis and generally applicable to other metabolites and proteins. Fig 1: Schematic of the UCR-ISB method for detecting fatty acid uptake from single cells.  

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.  

Researchers at the University of California, Davis have developed a new method of in utero gene editing through lipid nanoparticle delivery of mRNA gene editors.

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.

The inventors have developed a genome editing therapy for bone marrow failure (BMF) in people living with dyskeratosis (DC). This technology includes two novel endogenous, isogenic models to study TINF2-DC mutations.Human embryonic stem cells (hESCs) engineered to carry the TIN2-DC T284R mutation recapitulated the short telomere phenotype observed in DC patients. Yet, telomeres in TINF2-DC hESCs did not trigger DNA damage responses at telomeres or show exacerbated telomere shortening when differentiated into telomerase-negative cells. Disruption of the mutant TINF2 allele by introducing a frameshift mutation in exon 2 restored telomere length in stem cells and the replicative potential of differentiated cells. The inventors also established in vitro and in vivo human hematopoietic stem cell (hHSC) models to assess the changes in telomere length and proliferative capacity upon the introduction of TERT and TINF2 editing. In addition, the inventors demonstrated that editing at exon 2 of TINF2 that restored telomere length in hESCs could be generated in TINF2-DC patient HSCs. These experiments nominate TINF2 as a target for: CRISPR/CAS9 to elongate telomeres in patient with TINF2 mutations,CRISPR/CAS9 to elongate telomeres with other mutations causing TBD, and chemical interventions to elongate telomeres in general.BACKGROUNDBMF is a major cause of morbidity and mortality in DC and other telomere biology disorders (TBDs). Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for bone marrow failure.   

The inventors have demonstrated human milk oligosaccharides (HMOs) can be generated in transgenic plants, expressing a variety of genes used in nucleotide sugar biosynthesis and HMO biosynthesis. Production of human milk oligosaccharides in plants has not been presented previously and has advantages over current production methods.    

This invention is a biodegradable hydrogel mixed with minerals/chemical substances to slowly release ions/salts into the nearby aqueous waterbody through gradual abrasion of surface gel layers performed by underwater current.