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Micron-resolution malleable strain and pressure sensor

Scientists at UC Irvine have developed a sensitive, customizable, and user-friendly sensor for (1) strain detection as a result of cellular movement, (2) micro-fluidic device pressure detection, and (3) real-time monitoring of valve statuses in microfluidic chips. This research tool will provide new insights regarding cellular biophysics.

Three-dimensional organoid culture system for basic, translational, and drug discovery research

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

(SD2022-401) Dynamic Counterbalance to Enable Chronic Free-behaving Research with Small Animals

Researchers from UC San Diego have created a system to enable animal model research by reducing the physical impact of weight introduced by body worn or implanted instrumentation. It does so by dynamically counterbalancing the force introduced by the additional mass of the instrumentation. Together the dynamic counterbalance system, dynamic adjustment arm, and dynamic pulley provide a low cost system that addresses several of the pressing weight constraints of chronic small animal experiments. Together they will enable researchers to conduct experiments that would not have been possible due to weight restrictions of existing recording instruments.

A neuronal circuit analysis platform for drug discovery

Researchers at UC Irvine have characterized an electrophysiological-based drug discovery approach that offers a new modality with which to screen potential therapeutics and characterize mutations. This new level of analysis utilizes elements that are shared between rodents and humans, improving upon the uncertainties associated with rodent behavior. It also incorporates the full complexity of operations in a single assay, while rapidly specifying site(s) of action, thereby accelerating R&D for psychiatric illnesses.

Small molecule drug leads for p53 mutant cancers

Researchers at UC Irvine have used a computationally powered method to identify small molecule drug leads that exhibited anti-cancer activity in a human-cell-based assay. These small molecules and the approach used to find them will accelerate the research and development of anti-cancer therapeutics.

Biological and Hybrid Neural Networks Communication

During initial stages of development, the human brain self assembles from a vast network of billions of neurons into a system capable of sophisticated cognitive behaviors. The human brain maintains these capabilities over a lifetime of homeostasis, and neuroscience helps us explore the brain’s capabilities. The pace of progress in neuroscience depends on experimental toolkits available to researchers. New tools are required to explore new forms of experiments and to achieve better statistical certainty.Significant challenges remain in modern neuroscience in terms of unifying processes at the macroscopic and microscopic scale. Recently, brain organoids, three-dimensional neural tissue structures generated from human stem cells, are being used to model neural development and connectivity. Organoids are more realistic than two-dimensional cultures, recapitulating the brain, which is inherently three-dimensional. While progress has been made studying large-scale brain patterns or behaviors, as well as understanding the brain at a cellular level, it’s still unclear how smaller neural interactions (e.g., on the order of 10,000 cells) create meaningful cognition. Furthermore, systems for interrogation, observation, and data acquisition for such in vitro cultures, in addition to streaming data online to link with these analysis infrastructures, remains a challenge.

Hybrid Emission Tomography System and Methods

Common nuclear imaging techniques include computed tomography (CT), single photon emission CT (SPECT), and positron emission tomography (PET). PET differs from other nuclear imaging techniques in that it can visualize both functional and biological activities, including detection of metabolism within human tissues. PET is especially good for imaging patients with cancer, or brain or heart conditions. At low energies, when positrons collide with electrons near the radionuclide decay, Gamma rays (annihilation photons) are created. Gammas originating from the same electron-positron annihilation are generated exclusively in an entangled Bell state. Gammas which do not share an annihilation origin event, such as randoms, are not entangled. Additionally, a gamma which undergoes an internal scatter becomes decoherent (unentangled) from its pair, such as the gammas found in the scattered coincidence pairs. Scattered and random events degrade the image quality. Recently, quantum-based techniques utilizing entanglement of annihilation photons has been recognized as one approach to address scatter and random and to optimize the signal to noise (SNR) ratio.

Software Tool for Predicting Sequences in a Genome that are Subject to Restriction or Other Surveillance Mechanisms

Many genomes encode Restriction-Modification systems (RMs) that act to protect the host cell from invading DNA by cutting at specific sites (frequently short 4-6 base reverse complement palindromes). RMs also protect host DNA from unfavorably being cut by modifying sites within the host DNA that could be targets by the host’s own surveillance enzymes. It is also not unusual to find that these enzymes are adjacent to each other in the host genome. Traditional approaches to understanding these sites involve finding a methylase that is typically adjacent to a restriction enzyme, and then extracting DNA, expressing protein and then testing DNA sequence for evidence of cutting. In certain laboratory research (e.g., programs that involve transforming DNA/RNA) it may be desirable to more comprehensively understand the sequences being surveilled by the host. Moreover, it may be desirable in certain laboratory research to know/predict which surveillance enzymes are present in a genome in order to affect cell transformation efficiency through evasion of those sequences.

High-Throughput Discovery Of Bipartite Or Tripartite Crispr-Based Epigenetic Editors

Currently, conventional methods of epigenome editor discovery require time and labor-intensive construct development, which is typically performed in low-throughput arrayed formats. The platform bypasses current time/labor constraints (and without reliance on construct barcodes) to facilitate the identification of an optimal gene modulator in a single experiment.

Hyperspectral Microscopy Using A Phase Mask And Spectral Filter Array

Hyperspectral imaging, the practice of capturing detailed spectral (color) information from the output of an optical instrument such as a microscope or telescope, is useful in biological and astronomical research and in manufacturing. In addition to being bulky and expensive, existing hyperspectral imagers typically require scanning across a specimen, limiting temporal resolution and preventing dynamic objects from being effectively imaged. Snapshot methods which eliminate scanning are limited by a tradeoff between spatial and spectral resolution.In order to address these problems, researchers at UC Berkeley have developed a hyperspectral imager which can be attached to the output of any benchtop microscope. The imager is compact (about 6-inches), and can achieve a higher spatial resolution than traditional snapshot imagers. Additionally, this imager needs only one exposure to collect measurements for an arbitrary number of spectral filters, giving it unprecedented spectral resolution.

Novel EphA4 Agonists for the Treatment of ALS

Researchers at the University of California, Riverside (UCR) in collaboration Nationwide Children’s Hospital  have developed and characterized small peptidomimetics that act as EphA4 agonists. Given ALS is a heterogeneous disease, astrocytes reprogrammed from the fibroblasts of patients with sporadic and SOD1-linked ALS (iAstrocytes) were cultured with MNs and the UCR/Nationwide EphA4 agonists.  As seen in Fig. 1, these small agonistic peptidomimetics decrease MN death in iAstrocytes derived from sporadic ALS (sALS) cells.     

Compositions and Methods for Genome Editing

RNA-mediated adaptive immune systems in bacteria and archaea rely on Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) genomic loci and CRISPR associated (Cas) proteins that function together to provide protection from invading viruses and plasmids. Genome editing can be carried out using a CRISPR-Cas system comprising a CRISPR-Cas effector polypeptide and a guide nucleic acid, such as a guide RNA. However, unintended chromosomal abnormalities following on-target genome editing, such as chromosome loss, are potential concerns for genome editing. UC Berkeley researchers and others have developed a method to modulate the expression levels of the DNA damage response factor p53 in order to mitigate chromosomal abnormalities that occur after genome editing by nucleases like Cas9. The invention provides treatment methods by generating a modified cell and then administering the modified cell to an individual in need thereof and compositions having a CRISPR-Cas effector polypeptide, a guide nucleic acid, and an agent that increases the level of a p53 polypeptide in a mammalian cell.

Improved system for imaging of large biological samples in high refractive index solutions

Novel system for imaging of specimens in high refractive index solutions on the Zeiss Z.1 fluorescence light sheet microscope. System will allow for deep imaging of large and intact biological samples (i.e. mouse brain) for enhanced optical resolution and faster imaging speed.

DP-L4056 Prophage-Cured Strain Of Listeria Monocytogenes

DP-L4056 is a prophage-cured strain of Listeria monocytogenes based on wild-type strain 10403S. A prophage is a bacteriophage genome that is integrated into a bacterial genome. It remains latent until activation by an external factor, and activation leads to production of new bacteriophage particles that lyse the bacterial cell and spread. Curing the prophages in Listeria monocytogenes strain 10403S, which is ubiquitous in the microbiology community as a wild-type reference strain, allows for more predictable engineering and performance of Listeria monocytogenes.

Spectral Fluctuation Raman Spectroscopy (SFRS)

The function of living tissue relies not only on its structure, but crucially on its dynamics at an array of timescales. Structural imaging of biological molecules at very high resolution has become routine in recent years, but these static snapshots provide little insight into the structural changes crucial for biological function. It is well known that changes in the geometry of macromolecules induce fluctuations in the Raman spectrum, but measurements of these fluctuations inherently suffer from poor signal strengths, meaning that dynamics at many timescales are obscured by the time-averaging necessary to obtain sufficient sensitivity.To address these problems, researchers at UC Berkeley have developed a method for probing the Raman spectrum, and hence dynamics of biological molecules at very high sensitivity and across timescales inaccessible to extant techniques. This technique, in fact, can in principle obtain arbitrarily fine spectral and temporal resolution, opening the door to, for example, probe everything from the dynamics of side chain rotations (picoseconds) to protein folding and domain motion (milliseconds).

Systems For Pulse-Mode Interrogation Of Wireless Backscatter Communication Nodes

Measurement of electrical activity in nervous tissue has many applications in medicine, but the implantation of a large number of sensors is traditionally very risky and costly. Devices must be large due to their necessary complexity and power requirements, driving up the risk further and discouraging adoption. To address these problems, researchers at UC Berkeley have developed devices and methods to allow small, very simple and power-efficient sensors to transmit information by backscatter feedback. That is, a much more complex and powerful external interrogator sends an electromagnetic or ultrasound signal, which is modulated by the sensor nodes and reflected back to the interrogator. Machine learning algorithms are then able to map the reflected signals to nervous activity. The asymmetric nature of this process allows most of the complexity to be offloaded to the external interrogator, which is not subject to the same constraints as implanted devices. This allows for larger networks of nodes which can generate higher resolution data at lower risks and costs than existing devices.

Portable Neural Network Enabled Biofluid Spectroscopy

Researchers at the University of California, Davis have developed a method of biofluid assessment capable of real-time monitoring as well as compatible with machine learning and neural network processing.

Generalizable and Non-genetic Approach to Create Metabolically-active-but-non-replicating Bacteria

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

Reducing Risk Of Aerosol-Transmitted Infection From Dental Ultrasonic Instrumentation

Pathogenic transmission of dental aerosol created by ultrasonic scaling is considered a major concern during dental procedures. Researchers at UC Irvine have developed a novel tool/method to address this concern by removing the created aerosol at the source.

High-Throughput Selection Platform to Obtain NMN+-Utilizing Enzymes Through Directed Evolution

Noncanonical redox cofactor-based biotransformation is an attractive low-cost alternative to traditional cell-free reductive biotransformation. However, engineering enzymes to utilize noncanonical redox cofactors has been challenging. Addressing this problem, researchers at UC Irvine have developed a high-throughput directed evolution platform that enables development of such enzymes with ~147-fold improved catalytic efficiency, which translates to an industry-viable total turnover number of ~45,000 in cell-free biotransformation without requiring high cofactor concentrations.

Discovery of Gene Overexpression Combinations to Improve Therapeutic T Cell Constructs with Pooled CRISPR Knockin Screens

Scientists at UCSF have developed a method for highly parallel testing of gene knockins/overexpression in combination with a cancer-specific T cell receptor (TCR) or chimeric antigen receptor (CAR). The method enables researchers to evaluate what constructs can improve anti-tumor efficacy of conventional T-cell therapies. 

Genome Editing via LNP-Based Delivery of Efficient and Stable CRISPR-Cas Editors

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. The programmable nature of these systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation. There is a need in the art for additional CRISPR-Cas systems with improved cleavage and manipulation under a variety of conditions and ones that are particularly thermostable under those conditions. UCB researchers created a set of efficient CRISPR-Cas9 proteins from a thermostable Cas9 from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) through directed evolution. The gene editing activity of the evolved mutant proteins was improved by up to four orders of magnitude compared to the wild-type GeoCas9. The researchers showed that the gene editors based on the evolved GeoCas9 can be effectively assembled into lipid nanoparticles (LNP) for the rapid delivery to different cell lines in vitro as well as different organs or tissues in vivo. The LNP-based delivery strategy could also be extended to other gene editors.  

A Broadly Neutralizing Molecule Against Clostridium Difficile Toxin B

Researchers at UCI have developed a family of recombinant protein therapeutics against Clostridium difficile designed to provide broad-spectrum protection and neutralization against all isoforms of its main toxin, TcdB. These antitoxin molecules feature fragments of TcdB’s human receptors (CSPG4 and FZD) which compete for TcdB binding, significantly improving upon existing antibody therapeutics for Clostridium difficile infections.

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