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IgEvolution: A Novel Tool for Clonal Analysis of Antibody Repertoires

Constructing antibody repertoires is an important error-correcting step in analyzing immunosequencing datasets that is important for reconstructing evolutionary (clonal) development of antibodies. However, the state-of-the-art repertoire construction tools typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction. Thus, although repertoire construction is a prerequisite for follow up clonal tree reconstruction, the existing repertoire reconstruction algorithms are not well suited for this task because they typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction.

Breast Milk Biomarkers for Child Chronic Health Disorders

Autism Spectrum Disorder (ASD) is a developmental disorder associated with difficulties in social interaction and communication as well as repetitive behavior. ASD is thought to be the result of genetic and environmental factors that affect approximately 1 in 59 children in the US, and 25 million people worldwide. The current method of diagnosis for ASD involves evaluations and tests performed by a team of specialists.  The latest forms of diagnosis can detect ASD as early as 18 months. However, more standard methods take until 4 years of age before the diagnosis of ASD is confirmed. There remains an unmet need to develop a reliable and accurate diagnostic methods for early detection for a child at risk with chronic and/or developmental disorders, such as ASD, so that an early intervention measures will be applied before the first symptoms appear.

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.

Potent and Selective Peptide Inhibitors for MMP-2

Prof. Min Xue and his colleague at the University of California, Riverside have developed peptide-based selective MMP-2 inhibitors with nanomolar activities. Unlike known MMP inhibitors, n-TIMP-2 and GM6001 that inhibit a broad spectrum of the MMP family, these peptide inhibitors do not exhibit off-target effects with other MMP family members such as MMP-9.  Fig. 1 shows how a proMMP2 inhibitor (orange) interferes with the protein-protein interaction (PPI) between proMMP2 and TIMP2 (tissue inhibitor of metalloproteinases 2). This PPI inhibition blocks the TIMP2-assisted proMMP2 activation process and thereby results in lower levels of active MMP2. Fig. 2 shows the novel UCR MMP-2 peptide binds to proMMP2 with an Kd of 2.3 nM and inhibits MMP2 activation with an IC50 of 20 nM.  

Light-Tunable Biopolymer Hydrogels

Brief description not available

Mechanisms and Devices Enabling Arbitrarily Shaped, Deep-Subwavelength, Acoustic Patterning

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a Compliant Membrane Acoustic Patterning (CAMP) technology capable of patterning cells in an arbitrary pattern at a high resolution over a large area.

Fusion Proteins and Fusion Ribonucleic Acids for Tracking and Manipulating Cellular RNA

There are currently no consolidated systems that can both upregulate and downregulate the translation of specific messenger RNA (mRNA) targets. Known methods to achieve targeted downregulation include anti-sense oligonucleotides (ASO) and short interfering RNAs (siRNA). However, both of these technologies function to destabilize a messenger RNA target and downregulate translation, rather than upregulate translation. There are few known methods to increase mRNA translation and these methods are not well characterized. As such, there is a need to provide compositions and methods for recruiting translational pre-initation complexes in trans and thereby control translation in cells and in gene therapy techniques. Currently, there are no consolidated systems that can both upregulate and downregulate the translation of specific messenger RNA targets.

Computational Cytometer Based On Magnetically-Modulated Coherent Imaging And Deep Learning

UCLA researchers in the Department of Electrical & Computer Engineering have designed and built a computational cytometer capable of detecting rare cells at low concentration in whole blood samples. This technique and instrumentation can be used for cancer metastasis detection, immune response characterization and many other biomedical applications.

TRM: HIF-1 alpha KO Mice (CRE)

Hypoxia-inducible factor 1-alpha is a transcriptional regulator of the adaptive response to hypoxia. When activated under hypoxic conditions, it can turn on over 40 genes involved in a variety of physiological activities. The dysregulation or alteration by mutation can lead to pathophysiology in areas of energy metabolism, cancer, cell survival and tumor invasion.

Assay for Chronic Wound Biofilm Disruptors

Dr. Manuela Martins-Green’s UCR laboratory has developed a new assay to identify medicines that disrupt chronic wound biofilms in patients.  A patient’s wound biofilm is collected with a sterile swab and the bacteria collected from the swab are cultured and identified.  The bacteria are then used singly or in combination, to make a biofilm in 96 well plates to then be used for high throughput screening using a multitude of antibiotics, chemical and small molecules that may be tested alone or in combination for their ability to disperse the wound’s biofilm. Fig. 1 shows the biofilm cultures from chronic wound patient isolates. The biofilm is made more easily visible by staining with crystal violet. Fig. 2 Different concentrations of an antimicrobial drug ranging from 3 to 20 mg/ml were applied at 0, 6, 12, and 24 hours after the biofilm cultures were initiated. When applied at time zero the bacteria will not grow or form biofilm. This is akin to application after debridement. When applied after the biofilm has been formed it will dismantle the biofilm when used at the right concentrations. Akin to treating without debridement.  

TRM: Tbx18-CreERT2 Mice

The TBX18 (T-box 18) transcription factor is a key player in the formation of the sinoatrial node (SAN) formation during embryonic development.

TRM: Floxed Caspase-8 Mice

The Casp8 gene encodes a cysteinyl aspartate protease that is an essential part of the caspase activation cascade initiated by death receptors but it is also involved in preventing death receptors, Toll-like receptors TLR3 and TLR4 and T-cell receptors from inducing necroptosis. Caspase-8 also is essential for mouse development.

TRM: ISL-1 Cre Mice

Insulin gene enhancer protein ISL-1 or ISL1 transcription factor, LIM/homeodomain is a highly conserved gene. It binds to insulin gene enhancer sequences and is necessary for heart development

TRM: Islet-mER-Cre-mER Mice

Insulin gene enhancer protein ISL-1 or ISL1 transcription factor, LIM/homeodomain is a highly conserved gene (UniProtKB-P61371). It binds to insulin gene enhancer sequences and is necessary for heart development. In addition, it plays an essential role in the gene regulatory network crucial for retinal ganglion cell (RGC) differentiation.

TRM: Wnt-11 Knock-Out Mice

The Wnt gene family is composed of a large number of secreted glycoproteins involved in a wide variety of cell interactions ranging from early to adult stage that play a role in morphogenesis, paterning and development. In contrast to the Wnt/β-catenin signaling pathway which most Wnt proteins signal through, Wnt-11 signals via the Wnt/JNK pathway. A recent study demonstrates that the expression of secreted factor Wnt-ll is elevated in several types of cancer, including colorectal cancer (2019 R. M. Kypta et al.)

Manumeter for Monitoring and Assessing Upper Extremity Rehabilitation

After an injury or neurological event, a patient’s rehabilitation requires long-term assessment and monitoring, especially in the upper extremities that are important for everyday tasks.UCI researchers have developed the Manumeter to quantitatively assess and log a patient’s hand movements without external therapist intervention.

A Microplatform For Performing High Throughput, Multiplexed Assays On Adherent Cells

Systems and methods are providing for performing high-throughput, programmable, multiplexed assays of biological, chemical or biochemical systems. Preferably, a micro-pallet includes a small flat surface designed for single adherent cells to plate, a cell plating region designed to protect the cells, and shaping designed to enable or improve flow-through operation. The micro-pallet is preferably patterned in a readily identifiable manner and sized to accommodate a single cell to which it is comparable in size. Each cell thus has its own mobile surface. The cell can be transported from place to place and be directed into a system similar to a flow cytometer. Since, since the surface itself may be tagged (e.g., a bar code), multiple cells of different origin and history may be placed into the same experiment allowing multiplexed experiments to be performed.

Oldest-Old Mri Registration Template

MRI scans of patients/participants can be compared to template scans in order to identify differences or changes in brain anatomy. However, the templates that are used are typically of young brains, which lack the atrophy that naturally occurs in the aged brain. UCI researchers have developed a template for oldest old images (90+ age group) that takes into consideration the natural anatomical changes that can occur with aging.

A New Cell-free Protein Expression System with three-fold higher protein yield in batch and continuous mode than existing systems

Researchers at the University of California, Davis have developed a method for preparing a bacterial cell lysate that results in higher protein expression than existing cell-free systems. The new whole-cell lysate system comes with additional advantages, including the ability to synthesize protein from linear DNA, directly amenable to continuous or flow-based reaction, and compatibility with existing manufacturing workflow.

Systems and Methods for Monodisperse Drop Generation and Use

UCLA researchers in the Department of Bioengineering have developed systems and methods to produce single particle, monodisperse droplets for use in digital assays, targeted drug delivery, and theranostics.

HRas Selective Depalmitoylating Drugs

HRas is a member of the Ras family of GTPases, which function as key regulatory proteins in cell differentiation, proliferation, and survival. Mutations in HRas are associated with several cancers, as well as Costello syndrome, a severe congenital disorder for which there is no cure. Therefore, there is significant interest in developing therapeutics which target HRas signaling. However, Ras proteins are challenging to target

A Microfluidic Single-Cell Pairing Array for Studying Cell-Cell Interaction in Isolated Compartments

Cell interactions are fundamental to biological processes. Microfluidics provides a reliable platform to study these intricate phenomena. The researchers have developed a microfluidic trapping array which efficiently pairs single cells in isolated compartments in an easy to operate manner to study cell-cell interaction, especially at single-cell level.

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.

TRM: Dishevelled Segment Polarity Protein 3 (Dvl3) Mutant Mice

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, migration, differentiation, stem cell renewal and the planar cell polarity (PCP) pathway. Mammals share three Dishevelled (Dvl) family members and while the roles of Dvl1 and Dvl2 have been described previously, the functions of Dvl3 have remained an area of active research. The lack of Dvl3 in mice affects the formation of the heart, neural tube, and inner ear and that the defects in these tissues are much more severe when the mice are deficient in more than one Dvl family member, indicating redundant functions for these genes. Congenital heart disease affects approximately 75 in every 1,000 live human births, and approximately 30% of these diseases are due to disruptions in the outflow tract, the region affected in mice lacking Dvl genes.

TRM:CRAMP Knockout Mice In The C57bl/6 Background

The mouse Camp gene is an ortholog of the human gene CAMP, which encodes the precursor of cathelicidin antimicrobial peptide LL-37 (or CRAMP in mouse). Expressed mucosal epithelial cells, circulating neutrophils, and myeloid bone marrow cells, Camp is an essential part of the first line of defense against infection. In addition to antimicrobial activity, cathelicidin antimicrobial peptide plays a role in NK cell-mediated tumor growth suppression, and when secreted by neutrophils acts, as an attractant for monocytes, promoting wound healing or angiogenesis. Mouse CRAMP is implicated in adaptive immune response regulation and can interfere with TLR function via interactions with hyaluronan. Mice deficient in CRAMP are more susceptible to experimentally induced necrotic skin infection with Group A Streptococcus, urinary tract infection with uropathogenic E. coli, Pseudomonas aeruginosa infection, and meningococcal Neisseria meningitidis infection.

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