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Photocurable Poly(ethylene glycol) as a Bioink for the Inkjet 3D Pharming of Hydrophobic Drugs

UCLA researchers in the Department of Bioengineering have developed a novel inkjet 3D pharming technique that is fast, customizable, and compatible with hydrophobic drugs.

Antimicrobial and Osteoinductive Hydrogel for Dental Applications

UCLA researchers in the Department of Chemical & Biomolecular Engineering developed osteoinductive and antimicrobial hydrogel adhesives for dental applications.

Design Random Heteropolymer To Transport Proton Selectively And Rapidly

Despite decades of effort, it remains challenging, if not impossible, to achieve similar transport performance similar to natural channels. Inspired by the known crystal structures of transmembrane channel proteins, protein sequence-structure-transport relationships have been applied to guide material design. However, producing both molecularly defined channel sizes and channel lumen surfaces that are chemically diverse and spatially heterogeneous have been out of reach. We show that a 4-monomer-based random heteropolymer (RHP) exhibits selective proton transport at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in the RHP leads to well-modulated segmental heterogeneity in hydrophobicity, which facilitates the single RHP chains to insert into lipid bilayers. This in turn produces rapid and selective proton transport, despite the sequence variability among RHP chains. We have demonstrated the importance of:the adaptability enabled by the statistical similaritythe modularity afforded by monomer chemical diversity to achieve uniform behavior in heterogeneous systems. 

Preserving Protein Function Via Statistically Random Heteropolymers

Protein-based materials have the potential to change the current paradigm of materials science. However, it still remains a challenge to preserve protein hierarchical structure and function while making them readily processable. Protein structure is inherently fluid, and it is this property that contributes to their fragility outside of their native environment. Through the use of rationally designed statistically random heteropolymers, it is possible to stabilize proteins at each hierarchical level and process them in organic solvents, a common need for materials fabrication. The chemical and architectural complexities of statistically random heteropolymers provide a modular platform for tunable protein-polymer-solvent interactions. This provides opportunities not offered by small molecule surfactants or amphiphilic block copolymers. Through evaluation of horseradish peroxidase and green fluorescent protein structure, we show that statistically random heteropolymers can stabilize enzymes. Allowing for activity retention when stored in organic solvent, over 80% activity was observed after 24 hours. Furthermore, horseradish peroxidase and chymotrypsin proteins, when encapsulated in statistically random heteropolymers, are still accessible to their substrates while remaining inaccessible to the denaturing organic solvent. Statistically random heteropolymers have potential in creating stimuli-reponsive materials and nanoreactors composed of proteins and synthetic materials.

Liquid Metal Enabled Multi-Functional Neural Probes with Ultra-Large Tunable Stiffness

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a novel multi-functional neural probe with ultra-large tunable stiffness for electrochemical sensing and chemical delivery in the brain.

New Bright Green Fluorescent Proteins

Fluorescent proteins (FP) have been widely used as research tools in both academia and pharma for many years.  Naturally occurring FP have been mutated to either be brighter, be monomers, and/or for easier folding and expression in cells.  The most common FP to date has been the green fluorescent protein (GFP) of the jelly fish Aequorea victoria which can be expressed in cells and fused with proteins of interest, and has proven to be an excellent tool to study protein localization, expression, signaling, etc. in real time via microscopy and other techniques. 

Prevention Of Liver Disease By Preventing Degradation Of SRSF3

The global increase in obesity over the past few decades has caused a corresponding increase in NAFLD and its more severe form non-alcoholic steatohepatistis (NASH). Both NAFLD and NASH are associated with liver insulin resistance, non-alcoholic cirrhosis, and for the development of HCC. HCC is currently ranked as the fifth most common cancer worldwide and has a high mortality. It usually arises after years of liver disease and inflammation either due to chronic hepatitis B or C virus (HBV/HCV) infection, or alcoholic and non-alcoholic cirrhosis. SRSF3 is the smallest member of the SR protein family that function to promote RNA splicing by recruiting components of the spliceosome at constitutive and alternatively spliced exons. SRSF3 has also been ascribed a number of cellular functions including controlling cellular proliferation, as it is regulated during G1/S by the E2F transcription factor and controls the G2/M transition of immortal rat fibroblasts.  Recent findings demonstrating that loss of SRSF3 triggers metabolic changes, hepatic fibrosis, and increased liver inflammation that are all features of early liver disease. The loss of expression of SRSF3 in the liver leads to chronic liver damage, fibrosis and eventually to hepatocellular carcinoma (HCC). In fact, SRSF3 is reduced in samples of human HCC as well as NAFLD, NASH and cirrhosis. SRSF3 protein levels are controlled in part by the conjugation of SRSF3 to an ubiquitin-like protein NEDD8 on Lys11, which results in its degradation by the proteasome in response to stress.

Biomimetic Conductive Hydrogels

UCLA researchers in the Department of Bioengineering have developed a novel electrically conductive scaffold system with a hyaluronic acid (HA)-based hydrogel for biomimetic research to treat spinal cord and other central nervous system (CNS) injuries.

Improved Highly Potent Specific Human Kunitz Inhibitor of Fibrinolytic Enzyme Plasmin

UCLA researchers in the School of Medicine have developed mutant polypeptides of the tissue factor pathway inhibitor-2 (TFPI-2) Kunitz domain 1 (KD1), which can serve as potent inhibitors of fibrinolysis.

Gelatin Methacryloyl Based Microneedle

UCLA researchers in the Department of Bioengineering have developed gelatin methacryloyl microneedles (GelMA MN) for minimally invasive, sustained transdermal drug delivery.

Reactive Oxygen Species (ROS) Resistant Platform Strains for Bioproduction

The survival of bacteria is associated with the ability to respond to changing environmental conditions. For example, during situations of environmental pressure (e.g. UV, heat, or drug exposure) ROS levels can increase, leading to damage of DNA, lipids and an initiation of signaling events that can lead to cell death. Fortunately, bacterial possess enzymes such as superoxide dismutase (SOD) and catalase enzymes, as well as other antioxidant agents that can reduce ROS. However, when the balance between the production and elimination of ROS is upset, it can have unwanted effects. Thus, the ability of bacteria to increase their tolerance to ROS would be beneficial to the cell’s survival.

TRM:Sox9CreER BAC Transgenic Mice

These transgenic mice express an inducible version of cre recombinase mice under the direction of a Sox9 promoter. They are suitable for performing cre-recombination in pancreatic ductal cells and their progenitors.

Use Of Non-Ionic Copolypeptide Hydrogels For Cell Suspension And Cell And Molecule Delivery

UCLA researchers in the Departments of Bioengineering, Chemistry and Biochemistry, and Neurobiology have developed novel copolypeptide hydrogel formulations for the delivery of cells and molecules to locations throughout the body, including the central nervous system.

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.

Hv1 Modulators and Uses

Researchers at UCI have engineered a class of Hv1 polypeptide modulators that selectively modulate Hv1 voltage gated channels while leaving other voltage gated channels unaffected. With no Hv1 modulators currently on the market, this class of Hv1 polypeptide modulators could provide solutions in birth control, autoimmune therapies, and tumor reduction.

Novel Non-Antibody-Based Chimeric Antigen Receptor Against HIV That Also Protects Cells From Infection

UCLA researchers in the Department of Medicine have developed a novel chimeric antigen receptor (CAR) that targets T cells against HIV while protecting T cells from HIV infection.

Novel Protease for Oncology and Inflammatory Diseases

The technology is a novel protease that reduces the ability of cells to respond to the inflammatory cytokine Tumor Necrosis Factor (TNF). High TNF levels have been linked to rheumatoid arthritis, Crohn’s disease and many types of cancers.

Treatment Of Lysosomal Storage Disorders

UCLA researchers in the Departments of Neurology have developed a novel treatment for Lysosomal-storage diseases (LSDs) with neurological impairment.

New Molecular Tweezers Against Neurological Disorders And Viral Infections

UCLA researchers in the Department of Neurology with an international team of scientists have developed several new molecular tweezer derivatives with novel synthesis methods that significantly improved the therapeutic efficacy and pharmacokinetic characteristics of the drug candidates.

Metabolite-Responsive Hybrid Biomaterials

Researchers have developed a “smart” biomaterial for drug delivery systems capable of responding to signature cancer metabolite concentrations in tumor environments. This response triggers the release of encapsulated drugs at a specific tumor target.

Flexible Wearable Sensors for Non-invasive Continuous Blood Pressure Monitoring

Researchers at UCI have developed a wearable, wristband sensor that can detect the pressure of the body’s pulse from the surface of the skin at the wrist. They can correlate this measurement to blood pressure and subsequently use this device for long-term continuous monitoring.

Illumination Device for Dynamic Spatiotemporal Control of Photostimulation

A programmable LED device that illuminates multiple spatial locations (termed wells) with user-defined light patterns whose intensity can be modulated as a function of space and time. The devices are used for optogenetic stimulation of tissue culture plates (24-well and 96-well) kept in a heated and humidified tissue culture incubator, as well as photopatterning of hydrogels. In brief, light from LEDs passes through optical elements that ensure uniform illumination of each well. Parameters of the optical system, such as LED configuration, optical diffuser elements, materials, and geometry, were modeled and optimized using the optical ray tracing software Zemax OpticStudio. An electronics subsystem allows programmed control of illumination intensity and temporal sequences, with independent control of each well. Spatial precision is conveyed through a photomask attached to the culture plate. The hardware design also includes a cooling system and vibration isolation to reduce heating and damage to the sample. Lastly, a graphical user interface (GUI) was used to wirelessly program the illumination intensity and temporal sequences for each well. The devices can thus illuminate 24 independent channels with visible, NIR, or UV light with intensity ranges of 0 to 20-100 microwatts per millimeter-squared with 16-bit intensity resolution, and a temporal resolution of 1 millisecond and spatial resolution of 100 microns. In summary, the device allows uniform illumination of multiple wells for multiplexed photoactivation or photopolymerization of various substrates (light-responsive bacterial or mammalian cells grown in tissue culture, hydrogels, dyes, etc) with user-defined patterns. The device can be combined with a robotic handler, microscope, spectrometer, etc, to enable high-throughput illumination and simultaneous recording of the sample.

Development of a New Biomarker for Diagnosis of Cardiovascular Disease: Monoclonal Antibody to Oxidized Cholesteryl Esters

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. There are several promising biomarkers that might provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high-sensitivity assays for cardiac troponin, and heart-type fatty acid binding potential help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death and many others. However, there is a high unmet medical need for the more specific biomarkers that reflect different aspects of the development of atherosclerosis. 

Development of Novel Fluorescent Puromycin Derivatives

Puromycin is an aminonucleoside antibiotic produced by the bacterium Streptomyces alboniger. Its mode of action is to inhibit protein synthesis by disrupting peptide transfer on ribosomes, leading to premature chain termination during protein translation. Puromycin blocks protein synthesis in both eukaryotes and prokaryotes and is routinely used as a research tool in cell culture. The native Puromycin is also used assays such as mRNA display. As such, derivatives have been synthesized in which the amino acid of the 3' end of adenosine based antibiotics is altered to change the compound's antibiotic activity. Other compounds have been synthesized with differing amino acids and functionalities to examine the effect it has on bacterial viability. The majority do not show useful absorption or emission profiles. What is needed is a method to track the compounds in biological systems.

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