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Strategy for in vivo Depalmitoylation of Proteins and Therapeutic Applications Thereof

The neuronal ceroid lipofuscinoses (NCLs), commonly grouped together as Batten disease, are the most common neurodegenerative lysosomal storage diseases of the pediatric population. No cure for NCL has yet been realized. Current treatment regimens offer only symptomatic relief and do not target the underlying cause of the disease. Although the underlying pathophysiology that drives disease progression is unknown, several small molecules have been identified with diverse mechanisms of action that provide promise for the treatment of this devastating disease. On this point, several researchers have reported the use of potential drugs for NCL patient lymphoblasts and fibroblasts, along with neurons derived from animal models of NCL disease. Unfortunately, most of these studies were inconclusive or clinical trials or follow-up results were not available. High concentrations employed and toxicity of the small molecules are clear disadvantages to the use of some of the corresponding derivatives as potential drugs. To circumvent these effects, development of nontoxic alkyl cysteines would be useful for the non-enzymatic and chemo-selective depalmitoylation of S-palmitoyl proteins, which hold good promise as an effective treatment for neuronal ceroid lipofuscinoses.

Probe Immune Checkpoint Self-Cancellation Using Reconstitution Method

Programmed cell death protein 1 (PD-1), is a protein found on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.   PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells)The PD-1 pathway, consisting of the co-inhibitory receptor PD-1 on T cells and its ligand (PD-L1) on antigen-presenting cells (APCs), is a major mechanism of tumor immune evasion. PD-1 and PD-L1 blockade antibodies have produced remarkable clinical activities against a subset of cancers. Binding between T cell-intrinsic PD-1 and APC-intrinsic PD-L1 triggers inhibitory signaling to attenuate the T cell response.   It is challenging to determine whether PD-L1 and PD-1 bind in cis on the same cell membrane, and if so, what is the functional consequence. This is because of the co-existence of cis and trans interactions at the cell–cell interface. Methods to decouple cis and trans-interactions are urgently needed.

Phage-Mediated Delivery Of Genes To The Gut Microbiota

UCSF researchers have developed a novel method of manipulating the gut microbiome via delivery of bacteriophages to selectively remove or modify members of an existing microbial community. 

Hydrodealkenylative C(Sp3)–C(Sp2) Bond Scission

UCLA researchers in the Department of Chemistry and Biochemistry have developed a new chemical reaction that combines ozone, an iron salt, and a hydrogen atom donor to enable hydrodealkenylative cleavage of C(sp3)–C(sp2) bonds in a widely applicable manner.

Predicting Cefixime Susceptiblity Using Molecular Genotyping

UCLA researchers in the David Geffen School of Medicine have developed a novel method to detect the susceptibility of Neisseria gonorrhoeae to the antibiotic cefixime.

Method To Implement A Crispr-Cas9 Copycat Gene Drive In Rodents

Currently, alleles at multiple loci in the mouse genome must be combined by Mendelian genetics in crosses of animals to one another to produce a desired compound mutant genotype. For example, to combine homozygous mutations at two loci, animals that are heterozygous for each gene must be produced by breeding, and these are subsequently crossed to one another. Since the frequency of homozygosity for each allele is 1:4 the frequency of homozygosity for both genes is 1:16. Since the average litter of mice is approximately 10 pups, and the generation time from conception to reproductive age is about 3 months, this requires a substantial number of animals and time. With the addition of each new locus (three, four, etc), the cost measured in animals, time, and money increases exponentially. These factors increase substantially more if two or more loci are genetically linked, which requires rare recombination events to combine engineered alleles on the same chromosome. The CRISPR-Cas9 gene drive system stands to revolutionize rodent breeding. If each desired allele is encoded as a gene drive element that contains an sgRNA designed to target the same genomic location in the wild type homologous chromosome, each locus will be “driven” to homozygosity in the presence of Cas9. Therefore, in order to combine three alleles, for example, a mouse with one gene drive element (A) would be crossed to a mouse that encodes Cas9. Offspring of this cross would then be crossed to mice carrying gene drive element B, and these offspring would be crossed to mice carrying gene drive element C. In the presence of Cas9 at each generation, these gene drive elements at three distinct loci will be converted to homozygosity such that 50% of offspring, those that inherit Cas9, will be triple homozygous after three generations, even if they are genetically linked loci. A CRISPR-Cas9 mediated gene drive leverages the native cellular mechanism of homology directed repair to copy a desired allele from one chromosome to another. This process can convert a heterozygous genotype to homozygosity in a single generation. While CRISPR-Cas9 gene drives have been implemented in two species of insects, flies and mosquitos, it has not been reported in any non-insect animal species. 

Drug Repurposing To Explore Novel Treatment For Cushing Disease

UCLA researchers in the Department of Medicine and the Department of Molecular and Medicinal Pharmacology have identified several small molecule reagents to treat Cushing disease.

Learning Predictive Models Of Drug Response That Translate Across Biological Contexts

Translating biomarkers from basic research to clinical utility involves transfer of information across a series of contexts (from cells to disease animal models to humans) in which data are progressively harder to obtain. It is known that biomarkers identified in cell lines often do not translate to clinical settings and that is one of the main roadblocks in Translational Medicine. Presently, the state-of-the-art machine learning models require a number of training samples. The inventors show that conventional machine learning models, such as Random Forest, Linear Regression Model, Nearest Neighbors, cannot achieve accurate predictions and therefore there is a need for more accurate models.

Biotinylated Ligand-Directed Targeting Lentiviral Vectors

UCLA researchers in the Department of Medicine have developed a novel method to conjugate targeting ligands on lentiviral vectors.  The method allows for selective transduction of mammalian cells types avoiding non-target organs.

Novel Non-Immunogenic Positron Emission Tomography Gene Reporter

UCLA researchers in the Department of Pharmacology and Department of Microbiology, Immunology, & Molecular Genetics have developed a novel positron emission tomography reporter gene to preferentially trap radiolabeled deoxycytidine analogs.

Non-Immunogenic Positron Emission Tomography Gene Reporter Systems

UCLA researchers in the Department of Pharmacology and Department of Microbiology, Immunology, & Molecular Genetics have developed a novel dual gene positron emission tomography reporter system for the enhanced labeling of cells in vitro and in vivo.

Method for the detection of specific cells in bodily fluids with a small fluorescent probe

Using standard cellular biology techniques, researchers at UCI have developed a method for detecting the cellular components of blood easily, cheaply, and quickly with accurate quantification using fluorescence techniques.

Very-Small-Nuclear Circulating Tumor Cell (vsnCTC) as a Diagnostic Biomarker of Visceral Metastasis in Advanced Prostate Cancer

UCLA researchers in the Department of Molecular and Medical Pharmacology have identified a novel biomarker that can be used to diagnose prostate cancer patients for the presence of visceral metastasis with 54% sensitivity and 100% specificity.

Device and Method for Microscale Chemical Reactions

UCLA researchers in the Departments of Bioengineering and Molecular and Medical Pharmacology have developed a passive microfluidic reactor chip with a simplified design that is less costly than existing microfluidic chips.

Method for Concentration and Formulation of Radiopharmaceuticals

Researchers at the UCLA Department of Medical and Molecular Pharmacology have developed a compact microfluidic device that is able to achieve rapid concentration and/or reformulation of PET tracers after HPLC purification.

Low-noise Low-power ADC for Direct Biopotential Recording in Neuroscience Applications

High-density multi-channel neural recording is critical to driving advances in neuroscience and neuroengineering through increasing the spatial resolution and dynamic range of brain-machine interfaces.  Neural signal acquisition ICs have conventionally been designed composed of two distinct functional blocks per recording channel: a low-noise amplifier front-end (AFE), and an analog-digital converter (ADC).  Hybrid architectures utilizing oversampling ADCs with digital feedback have seen recent adoption due to their increased power and area efficiency. However, input dynamic range (DR) is still relatively limited due to aggressive supply voltage scaling and/or capacitive sampling noise.

Thermodynamic Integration Simulation Method for Filling Molecular Enclosures Using Spliced Soft-Core Interaction Potential

Researchers have developed a simulation method to determine the properties of molecular enclosures based on slow growth thermodynamic integration (SGTI).

Vascularized Tissue Engineering

Tissue engineering and/or regenerative medicine are fields of life science employing both engineering and biological principles to create new tissues and organs and to promote the regeneration of damaged or diseased tissues and organs. Major advances and innovations are being made in the fields of tissue engineering and regenerative medicine and have a huge impact on three-dimensional bioprinting (3D bioprinting) of tissues and organs. 3D bioprinting holds great promise for artificial tissue and organ bioprinting, thereby revolutionizing the field of regenerative medicine. One of the main roadblocks of 3D bioprinting tissues is the lack of efficient techniques to generated vascularized structures. This is critical for grafting applications as limited supply of nutrients and oxygen resulting in premature death of cells.

DARTS: Deep Learning Augmented RNA-seq Analysis of Transcript Splicing

Researchers led by Yi Xing have developed a novel deep learning algorithm to detect alternative splicing patterns in RNA-seq data

Easy to Wear Dry EEG Sensors for Human–Computer Interactions

Measurements based on electroencephalogram (EEG) are made by placing electrodes over a human scalp to apply and receive electrical signals. Various implementations of EEG sensors are available. The electroencephalogram (EEG) has recently gained popularity for use in various non-clinical studies but still lacks any robust, single application outside well-controlled laboratory environments. As the limitations of EEG are mostly due to the low spatial resolution, using multiple bio-sensing modalities proves to be better performing than EEG alone

CRISPR-CAS EFFECTOR POLYPEPTIDES AND METHODS OF USE THEREOF (Cas14 Type)

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of Cas 14 protein.  Site-specific binding and/or cleavage of a target nucleic acid (e.g., genomic DNA, ds DNA, RNA, etc.) can occur at locations (e.g., target sequence of a target locus) determined by base-pairing complementarity between the Cas14 guide RNA (the guide sequence of the Cas14 guide RNA) and the target nucleic acid.  Similar to CRISPR Cas9, Cas14 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.    

Carborane-Based Histone Deacetylase (HDAC) Inhibitors

UCLA researchers from the Department of Chemistry & Biochemistry have developed a new class of Histone Deacetylase (HDAC) inhibitors that can be tuned for isoform specificity and other properties.

CRISPR-CAS EFFECTOR POLYPEPTIDES AND METHODS OF USE THEREOF

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of Cas 12 protein.  Site-specific binding and/or cleavage of a target nucleic acid (e.g., genomic DNA, ds DNA, RNA, etc.) can occur at locations (e.g., target sequence of a target locus) determined by base-pairing complementarity between the Cas12 guide RNA (the guide sequence of the Cas12 guide RNA) and the target nucleic acid.  Similar to CRISPR Cas9, Cas12 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.    

Mobile Microscopy Camera

A portable camera device that combines fluorescent imaging with optical sectioning capability of microscopic samples and wireless data transfer. This 3D sectioning imaging system and fluorescent detection will detect bacteria for ease use in remote areas for on-site diagnosis and will connect to a smartphone. The technology will lead to significant improvements in public health.

Low-Cost And Portable Uv Holographic Microscope For High-Contrast Protein Crystal Imaging

UCLA researchers in the Department of Electrical Engineering have developed an on-chip UV holographic imaging microscope that offers a low-cost, portable, and robust technique to image and distinguish protein crystals from salt crystals.

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