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OptoPlates: Programmable LED Devices for Tunable Illumination of Tissue Culture Plates

A programmable, standalone LED array that unlocks new potential for both real-time activation of proteins and visualization of cells during high-throughput screening. This device can be used in such advanced research techniques as optogenetic activation, photoconversion, photobiology, and drug screening.

Generation Of Human Beta Cell Equivalents From Pluripotent Stem Cells In Vitro

This invention describes a robust method to generate functional human beta cell equivalents from pluripotent stem cells in vitro for wide applications in basic research, drug and toxicology screens and as a diabetes cell therapy.

A Novel Method to Functionally Screen Pooled Libraries of Synthetic, Genetically-encoded Signaling Molecules and Systems

This technology contains a method of screening pooled libraries of synthetic, genetically-encoded constructs and assessing functional effects of the variants on cell activity. This approach can be used to screen a large number synthetic signaling molecule that alters cell behavior and function.

Drug Target Discovery Using Pooled CRISPR Genetic Screening Assay

This invention provides a method for easily developing a genetic screen for drug target identification in human primary cells.

SEQUENCING OF NUCLEIC ACIDS VIA BARCODING IN DISCRETE ENTITIES

This invention identifies a method to prepare nucleic acid barcodes using microfluidic methods; allowing for high throughput analysis of many individual samples.

Generation of Metagenomic Next-generation Sequencing Libraries Optimal for Long-read Sequencing Technologies

This invention is a technology that prepares physical long-read fragments from short-read metagenomic libraries that can be sequenced quickly and efficiently using long-read next-generation sequencing technologies. As of this time, there are no existing commercially available technologies that can offer this advantage.

NOVEL, HIGH THROUGHPUT METHOD TO MEASURE THE FUNCTIONAL ACTIVITY OF MULTIPLE KINASE ENZYMES SIMULTANEOUSLY

This invention enables the direct measurement of the comprehensive activity of multiple kinase enzymes simultaneously, thereby enabling the mapping of functional kinase networks.   

Methods And Reagents For Live Biopsy

This invention identifies a set of antibodies that allow direct imaging of immune cells in a tumor biospecimen.

INFRARED FLUORESCENT PROTEASE REPORTERS FOR DEEP TISSUE IMAGING

This invention includes the design and use of protease imaging reporters which can be detected in deep tissue. These can be used to monitor the effects of protease inhibitors, proteases and protease mediated processes including apoptosis related to the treatment of disease states such as cancer.

Genome-Scale CRISPR-Mediated Control of Gene Expression

This invention is a novel method of controlling gene expression at genome scale using CRISPRi/a, which provides for highly specific and robust induction or repression of transcription.

Tunable, Modular Control of Multi- Gene Expression Using CRISPR RNA- Mediated Technology

A novel advancement of CRISPR technology which allows tuning the magnitude and direction of gene expression levels independently at each individual gene target.

NOVEL METHOD OF DETECTING O-SULFONATION POST-TRANSLATIONAL MODIFICATIONS IN PROTEINS

This invention is a novel technique that detects the serine and threonine sites of O-sulfonation on post-translationally modified proteins. Using novel chemistry, sulfonyl functional groups can be enzymatically labeled with this technology and easily detected by mass spectrometry.

A SYSTEM TO IDENTIFY NOVEL UBIQUITIN LIGASE SUBSTRATES

Non-covalent macromolecular interactions of proteins with lipids, nucleic acids, small ligands, and other proteins underlie a vast majority of biological processes. The transient nature of these interactions makes it difficult to use traditional methods to detect specific non-covalent macromolecular interactions. Ubiquitination is one such macromolecular interaction cascade that results in the addition of ubiquitin to a wide variety of substrate proteins. The addition of ubiquitin represents an important regulatory mechanism in the cell to modulate global protein levels and specific signal transduction cascades. Ubiquitination of a substrate protein occurs as a result of a pyramidal cascade involving the sequential action of three classes of E1, E2, and E3 proteins. In general, a small number of E1-activating enzymes transfer ubiquitin to a limited number of E2-conjugating enzymes that in turn function together with a large number of E3-ubiquitin ligases to ubiquitinate a variety of substrate proteins. In humans for example, only two E1 enzymes can transfer ubiquitin to more than three-dozen E2-ubiquitin conjugating enzymes, which in turn can partner with several hundred E3-ligases to ubiquitinate thousands of target substrates. The pervasive use of ubiquitination as a regulatory mechanism in the cell, coupled with the transient nature of the interaction between E3-ligases and their respective substrates, presents the unique challenge of accurately identifying the appropriate E3-ligase/substrate pairs to better understand normal and pathological cellular processes.  

A Novel Reporter System that Detects DNA Mutations in Pluripotent Stem Cells

DNA mutation events (gene rearrangements, base-pair substitutions) cause genomic instability, and can lead to cell death or cancer. These events also potentially lead to gene dysfunction and genetic disorders. DNA mutation events have many possible causes, such as inherited mutations in genes involved in genomic integrity, or exposure to environmental toxins. Human stem cell technology, in which stem cells can be differentiated into any cell type in the body, has the great potential to advance the discovery of therapeutics for unmet medical needs. However, recent reports indicate increased DNA mutation frequency in stem cells, which limits their potential use for discovery or therapeutic purposes. Therefore, technologies that enable the detection of the different types of DNA mutations would advance the characterization and selection of human stem cell lines for discovery or therapeutic purposes, and help characterize the mutagenic potential of environmental toxins.

Acat-2, A Second Mammalian Acyl Coa:Cholesterol Acyltransferase That Is Involved In Cholesterol Metabolism

Acyl-COA: cholesterol acyl transferases or ACAT is an enzyme that catalyzes the esterification of cholesterol to form cholesteryl ester. Minimally, ACAT-mediated formation of cholesteryl ester from cholesterol prevents the toxic accumulation of excess cholesterol in a cell and maintains a free diffusion gradient across the cell membrane, particularly in the small intestine. In addition, the assembly and secretion of Apolipoprotein-B containing lipoproteins in the liver and intestines is thought to be dependent on the ACAT-mediated formation of cholesteryl esters from cholesterol. In steroidogenic tissue such as the adrenal glands, ACAT activity produces cytosolic droplets loaded with cholesteryl esters from which they can be mobilized as cholesterol substrates for the generations of steroids. Furthermore, macrophages that accumulate cholesteryl ester in cytosolic lipid droplets as a result of ACAT activity appear foamy and are a characteristic early indicator of atherosclerotic lesions. Animal models that completely lack ACAT protein are viable, albeit with tissue-specific reductions in cholesteryl ester, suggesting that another ACAT enzyme is present in these animals.

Novel, Immunogenic Epitopes for use in an HIV Vaccine

The Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate maker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently focused their attention on so-called cryptic peptides of HIV.  Cryptic peptides are non-functional HIV proteins that are produced due to translational errors that occur in HIV-infected cells.  Because these cryptic peptides are commonly produced and then presented on the surface of the HIV-infected cells, it is thought they may be good surrogate markers and targets for any HIV-infected cell.

Novel Biomarkers for Autoimmune-mediated Lung Disease

Interstitial lung disease (ILD) is a common manifestation of systemic autoimmune diseases such as rheumatoid arthritis (RA), lupus and scleroderma, which can lead to inflammation and scarring of the lung and, consequently, to hypoxemia, pulmonary hypertension and death.  It is estimated that ILD occurs in approximately 15 percent of patients with RA.  Very little is known about how ILD disorders arise and what role loss of immune tolerance plays in ILD development.  Presently, there are no validated lung-specific autoantigens for diagnosis of autoimmune-mediated lung disease.  Current options for ILD treatment are limited to powerful immunosuppressive medications with significant side effects.  Identification of novel pulmonary biomarkers is sorely needed to develop better diagnostic methods and therapies for ILD.

Novel, Real-Time Method for Brain Mapping

The ability to map important brain regions (e.g. sensory and motor cortex) is critical for surgical procedures that require precise information of neural activity so that neurosurgeons can safely operate. The current state of the art relies on electrical cortical stimulation that is not only inefficient but also relies on electric shock thereby generating non-physiologic activity from the areas sampled, and such stimulation can also cause dangerous seizures. Furthermore, electrical stimulation mapping frequently misrepresents and underestimates the extent of the functional cortex, leading to neurologic impairments in patients despite comprehensive mapping. Additionally, inaccurate mapping by electrical stimulation may also lead to incomplete resection of a tumor or epilepsy focus to preserve the tissue whose function is not clearly identified or incomplete, resulting in tumor regrowth or continued intractable seizures, respectively.   What neurologists and neurosurgeons need is a safe and efficient functional brain mapping tool that will allow them to accurately perform cortical tissue resections without compromising critical brain regions.

Apicoplast-Deficient, Attenuated Strains of Plasmodium for Use as Malaria Vaccines

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans.

Efficient genetic system for high throughput screening of new compounds that modulate activity of potassium ion channels

Researchers at UCSF have developed a novel and efficient genetic high throughput screening system for discovery of small molecule modulators that either activate or inhibit K2P potassium channel activity. Such modulators could be used for treating diseases such as chronic pain, depression, and also to modulate responses to general anesthesia.

A safe and reliable device for endovascular biopsy

UCSF inventors have developed a safe endovascular biopsy device for extraction of endothelial cells from the blood vessel wall.

METHODS AND DEVICES FOR HIGH THROUGHPUT, HIGH SPECIFICITY SORTING OF SOMATIC, GAMETES, AND STEM CELLS

Cells have long been sorted by various means including through electrokinetic sorting, differential uptake of chemicals, magnetic antibodies specific to the target cell surface, and flow-cytometry assays. A key limitation to these methods is that they are either not sufficiently specific to isolate dead cells from live cells or they render the sorted cells unusable for clinical applications. UC investigators have developed a cell sorting platform that allows sorting live cells from minimally viable cells and dead cells, while minimizing the risk of damage to the live cells during the sorting process. This process does not require that properties of the cell be known a priori, and allows for greater flexibility of sorting patterns. This platform is high-throughput and retrieves groups of sorted cells.

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