The majority of patients who die of cirrhosis die due to a complication of increased portal venous pressure. The hepatic vein pressure gradient (HVPG) is a prognostic indicator for long term survival in cirrhosis, and can also reflect progression of disease in the pre-cirrhotic stage. Patients that present with cirrhosis often hemorrhage after medical procedures. There is no test to determine whether patients have portal hypertension other than performing a screening esophogo-gastro-duodenoscopy (EGD), and patients undergoing this upper endoscopy do so at a cost of $3,000-$10,000 per procedure. A diagnostic test that can exclude patients at risk will eliminate the need for EGD in those patients. (more...)

For decades, scientists have used ultrasound (US) for non-invasive medical imaging. More recently, researchers have shown that US can also stimulate brain activity, offering the prospect of treating neurological disorders such as Alzheimer's disease and Parkinson's disease without surgery or genetic alteration. These two conditions alone afflict over 6 million patients in the United States, with the figure trending upwards as life expectancies rise. However, the underlying molecular mechanisms that drive this low intensity focused ultrasound-induced neuromodulation are not well-defined. Currently available systems for US studies are severely constrained, typically placing a single transducer next to a single cell culture plate or flask, rather than focusing transducers on individual cell culture wells. There is a pressing need for a new high throughput system- one which permits scientists to experiment with a high volume of cells simultaneously, using a wide range of ultrasound parameters, varying from one well to another.      (more...)

Rapid and efficient detection of mutagenic and carcinogenic potential in chemical materials has become a priority for the consumer, chemical, and pharmaceutical industries.  In fact, not detecting mutagenicity early in development is a major liability, particularly for drug companies.  As a result, in vitro carcinogenic assays – with the benefits of low cost, reduced use of animal tests, and faster results – are of significant interest to both companies and testing labs, and their use is expect to grow in the predictive toxicity testing market, which was valued at more than $1.3 billion globally in 2010. The Ames test, developed in the 1960s, is a widely adopted biological assay for the detection of mutagenic compounds and has been employed by the pharmaceutical, agricultural, and petro-chemical industries. However, the test has numerous limitations owing to its reliance on bacterial growth and is sub-optimal in predicting mutagenicity in higher organisms (high incidence of false-negatives).  As a result, other tests have been developed using human cell lines to detect DNA damage, the primary cause of mutagenicity. Yet these tests are limited by their inability to directly measure DNA damage, which also leads to a high false negative rate. Thus, an in vitro assay that can quickly and directly measure DNA damage would greatly improve the efficiency and reliability of carcinogen and mutagen testing of chemicals.     (more...)

Nuclear Magnetic Resonance (NMR) spectroscopy is a widely-utilized method for analyzing small molecule compositions. It is among the most sensitive techniques available and has great potential for studying metabolic profiles in living organisms. Since variations in the metabolite concentrations are indicative of many disease states, NMR can be a powerful diagnostic tool. In practice, however, this requires sensitivity still beyond the capabilities of current instruments. As a result, using NMR for diagnostic purposes has been limited to academic research. A key component responsible for the sensitivity is the NMR probe, which holds the sample as it is inserted into the magnetic field. Advancing the probe design is critical to enabling practical medical applications of NMR. (more...)

Cell-based systems for in vitro biomarker profiling of drug efficacy or discovery. (more...)

The invention (software) relates to methods for estimating the strength of the hip (the proximal femur) for assessing osteoporosis and the risk of hip fracture. It can also be used for other applications for which the strength of the hip is important. In this context, the strength of the proximal femur is defined as the maximum force that can be applied to the femoral head before the bone will break and no longer be able to support the applied force. It has been demonstrated previously that proximal femoral strength can best be estimated by combining quantitative CT scan imaging, which provides the bone geometry and density at each point in the bone, with a structural engineering technique called finite element (FE) analysis. In essence, this numerical technique subdivides a structure into many smaller parts (finite elements) which, together, explicitly represent the complex material heterogeneity and 3-D bone geometry as a mathematical model. Force or displacement is then mathematically applied to represent a specific loading condition, e.g. single-limb stance or a particular type of fall onto the greater trochanter. When the FE model is analyzed, stress and strain throughout the bone structure are computed. This information is used in conjunction with material failure criteria in various ways to estimate the strength of the proximal femur under the particular loading condition. Collectively, this technique is called, “subject-specific CT scan-based finite element modeling for calculation of proximal femoral strength." This invention disclosure pertains to a specific improvement to techniques for patient-specific FE modeling for predicting the strength of the proximal femur for loading from a fall onto the greater trochanter (more...)

ANCCA as a marker and therapeutic target in breast cancer (more...)

A number of diabetogenic stimuli interact to influence insulin promoter activity. High-Throughput Screening (HTS) for insulin promoter modulators has the potential to reveal novel inputs into the control of that central element of the pancreatic β-cell. HTS for insulin promoter modulators can both serve to identify compounds that can serve as a treatment to diabetes as well as identify unintended side effects of insulin promotion in other drug candidates. (more...)

University of California, Davis researchers have developed a computer algorithm that precisely measures the extent of brain atrophy on structural MRI images over successive time intervals.  The method achieves higher sensitivity and specificity than previous algorithms.  Due to the bias in images and in conventional algorithms, a penalty term reduces the algorithm sensitivity and localization, leading to an under-reporting of real change.  This algorithm restores sensitivity without losing specificity by also incorporating a priori tissue boundary information. (more...)

UCI researchers have fabricated a single pore membrane with an undulating pore diameter and tested its ability to differentiate particle shape, size and ductility. This new membrane and technique has demonstrated the ability to count/sort particles at order of magnitude higher concentrations than currently available Coulter counters.. (more...)

Researchers at University of California, Davis have discovered a nanophotonic device that reduces limits of detection of an immunoassay by orders of magnitude. (more...)

Researchers at the University of California, Davis campus have developed a miniature device for separating or detecting many different chemical species.  The device features an ion passage formed between a top and bottom containing discrete electrodes.  The low power consuming DC voltage-driven, hybrid device employs custom-tuned electric fields to manipulate ions for chemical analysis.  The device can be manufactured using low-cost microfabrication techniques. (more...)

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in adult American men, with an estimated 217,730 new cases diagnosed in the U.S. in 2010.  Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer.  However, elevated serum PSA can be present in other non-malignant conditions, such as benign prostatic hyperplasia and, therefore, PSA screening has a high false positives rate.  Active surveillance (AS) of prostate cancer is a current strategy that is used to reduce overtreatment by monitoring of low-risk patients with physical exams, PSA assesssments and repeat biopsies, and offering treatment to those with signs of progression.  However, nomograms that utilize these predictors of disease progression demonstrate an accuracy of only 61-79% in the clinic.  Given the limitations of PSA and significant disease that can be used to categorize patients with localized prostate cancer and assist in treatment decision-making.  Several recent studies have shown that serum miRNA signatures have potential value as prognostic tools for prostate cancer. (more...)

Mutations and duplication of the X-linked MeCP2 gene are observed in several disorders, such as Rett Syndrome (RTT), Autism, severe neonatal encephalopathy, schizophrenia and X-linked mental retardation. As MeCP2 plays an important role in the pathogenesis of multiple mental disorders, the investigation of MeCP2 function and regulatory pathways may show promise for developing broad-spectrum therapies. (more...)

High-throughput, automated, large-scale mircoarry format assay in a short time frame and at low cost. (more...)

Opioid receptors are abundant in the central and peripheral nervous system and are the targets of both opiate drugs and a family of endogenous opioid peptides. Seminal work carried out by Dr. Evans' research group at UCLA on this receptor has led to key insights in the field of neuropharmacology. To date, the delta opioid receptor has been implicated in various diseases including, but not limited to, pain, depression, neuroprotection, drug abuse and impulse control disorders. Moreover, on-going work has hinted at additional roles for this critical receptor. A method for screening potential modulators of the delta opioid receptors would provide unparalleled insight into the development of targeted therapies against this key target. (more...)

Abdominal aortic aneurysm (AAA) is a severe human vascular disease resulting in progressive aortic dilation and eventual lethal rupture. Approximately one in every 250 people over the age of 50 will die of a ruptured AAA. While the success rate of surgical repair is high for aneurysms bigger than 5cm, reliable prediction of the asymptomatic disease remains elusive. Moreover, smaller instances of the disease cannot be easily diagnosed with radiography, or ultrasound, potentially resulting in silent growth and sudden rupture. Even CT and MRI will not be able to detect aneurysms at the early initiation stage that only involve molecular remodeling of the aortas. Thus, there is an urgent need for a more robust and sensitive method to predict AAA development at very early stages to enable better monitoring and treatment of the disease. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

HBV infection can lead to chronic infections that result in 0.6 million deaths per year worldwide by causing liver failure and cancer. Clearance of HBV infection is age dependent, with the majority of adult-acquired infections leading to spontaneous clearance, whereas infection in young children often leads to chronic infections. To study these early events of infection and immune activation that lead to HBV clearance or persistence, in vivo models are needed to screen and validate lead drug candidates. HBV cannot infect mice, however, researchers at UCSF have generated transgenic mouse models that mimic critical features of primary HBV infection observed in humans. (more...)

Huntington's disease (HD) is characterized by progressive deficits in motor control and cognitive deterioration. It is caused by an increase in CAG nucleotide repeats in the Huntingtin gene, resulting in an expansion of a polyglutamine region in the encoded Huntingtin protein (Htt). This mutant Htt protein is highly toxic to neurons and results in substantial cell death in the brain, but its mechanism of action is unknown. There is currently no treatment to prevent or palliate the progress of HD. Identification of clinically effective drugs that would decrease symptoms or increase survival would represent a major advance. (more...)

Thousands of severely disabled patients are unable to communicate due to paralysis, locked-in syndrome, Lou Gehrig’s disease, or other neurological disease. Restoring communication in these patients have proven a major challenge. Prosthetic devices that are operated by electrical signals measured by sensors implanted in the brain are being developed in an effort to address this problem.  Investigators at University of California at Berkeley have responded to this challenge by developing an algorithm to decode speech, including arbitrary words and sentences, using brain recordings from the human cortex.  a computational model is trained that determines how recorded electrical signals at specific brain sites represent different speech features, for example acoustic frequencies.  The trained model then takes as input novel brain recordings and outputs a set of predicted speech features.  Once these steps are accomplished, speech sounds are either directly synthesized or words are identified from the predicted speech features using statistical techniques.  The brain signal decoding algorithm can decode speech solely from brain signals and may permit communication via thought alone.    (more...)

The study of microbiomes can offer new insight into the origins of environmental changes, disease, immunological functions, and host physiological functions.  With as many as 1030 microbial genomes globally, characterizing the microbial composition of these assemblages is a challenge for current approaches.  Standard culturing techniques are successful in identifying only a small fraction of the microogranisms in nature.  A more direct profiling approach, such as sequencing, presents a complex problem for an already laborious task due to the sheer number of different species in a given sample and the degree of biomarker sequence homology between microbial members.  Confidently identifying the thousands of taxa present in a given sample and relating their relative abundance and distribution in these consortia to disease states is a significant challenge to current methods of detection.  Improved methods for designing nucleic acids, proteins, or other markers that can recognize specific organisms, or taxa are needed.  Also, improved methods for data analyses that allow detection and quantification of the members of microbial community at high confidence levels are also needed. (more...)

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 marker that could be used to target any HIV-infected cell regardless of its mutational status, enabling eradication of the virus. In this regard, scientists at UCSF have recently begun to take a closer look at Human Endogenous Retroviruses (HERVs) that are present in all human cells.  HERVs are a family of retroviruses found in the human genome and are thought to have originated from an ancient retrovirus that become permanently integrated with the DNA of its host's germ cells.  HERV viruses are inactive in normal cells but one type of HERV, HERV-K, is activated in HIV-infected cells.  The HERV-K proteins are presented on the surface of HIV-infected cells.  Because HERV-K is expressed in all HIV-infected cells, it is thought HERV-K antigens presented on the surface could be a good candidate to generally target any HIV+ cell. (more...)

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. (more...)

Researchers at the University of California, Davis have developed a new method of obtaining a library of sialyl Lewis x and other sialosides containing different sialic acid forms. This method utilizes engineered mutants of sialyltransferase PmST1. These novel mutants show lower donor hydrolysis activity and/or sialidase activity without compromising the sialyltransferase activity. (more...)

The diffuse optical spectroscopic imaging (DOSI) device is a tissue spectroscopy instrument designed to measure absorption and scattering properties of tissues. These absorption and scattering spectra are dependent upon the functional and structural composition of the tissue under study. The use of non-ionizing radiation probes the tissues below the surface non-invasively. While the idea of optical tissue spectroscopy is not unique, researchers at the University of California, Irvine have developed a unique compact modular platform that provides high portability yet retains the high information content of spectroscopic imaging of tissues. (more...)

THE SCREEN  Dr. Stephen Smale, Professor and Vice Chair of Microbiology, Immunology & Molecular Genetics at UCLA and colleagues have developed an improved cell-based screen for the identification of selective modulators of pro-inflammatory gene expression. The technology utilizes a macrophage cell line derived from either transgenic mice or differentiation of genetically modified embryonic stem cells. The resultant cell line contain two types of reporters, which allow small molecules that selectivity inhibit transcription of the inflammatory gene of interest to be accurately and easily separated from those that inhibit inflammatory gene expression more broadly. The technology is a significant improvement over conventional reporter gene assays that utilize cell lines stably transfected with a promoter-reporter gene plasmid containing a green fluorescent protein (GFP) or luciferase reporter gene. The stably integrated plasmids in these conventional reporter assays do not assemble into native chromatin and therefore do not behave in the same manner as an endogenous gene, resulting in erroneous screening results. The methodology developed by Dr. Smale and colleagues allows the same low cost, rapid and sensitive screening afforded by the conventional reported gene assays, but with the significant advantage that gene expression is measured in a native chromatin environment. This permits the identification of small molecules that are far more likely to modulate gene expression in vivo and be suitable for further development. A second major advantage of the methodology is offered by the inclusion of a second reporter cassette that allows non-selective inhibitors to be identified and excluded. Dr. Smale has initially developed and validated the screen using a bacterial artificial chromosome (BAC) for the IL12B gene, but the approach could readily be modified to screen for modulators of other genes of interest. THE INHIBITORS  A variety of existing and new small molecule inhibitors of IL12B transcription were identified using this approach, and were further validated using a primary cell assay. IL12B encodes the p40 subunit of the IL-12 and IL-23 cytokines; the p40 protein is the target of the Stelara antibody, a highly effective new therapy for the treatment of psoriasis and possibly other inflammatory diseases. The new compounds identified in the screens could be further developed into drugs to treat a variety of inflammatory conditions including inflammatory bowel disease, atherosclerosis, psoriasis and sepsis. Selective small molecules would have added advantages over antibody-based therapeutics of cheaper production, greater tissue biodistribution and the potential for oral administration. (more...)

UC Davis researchers from the NSF Center for Biophotonics and UC Davis Health System have developed a method of identifying and sorting cardiomyocytes derived from human pluripotent stem cells.  This method, based on second harmonic generation (SHG) - a nonlinear optical technique, does not require genetic modification of the cell or any exogenous labels to be used, which makes this an attractive technique for obtaining pure populations of cardiomyocytes under xeno- and vector- free conditions most appropriate for clinical and therapeutic use, as well for tissue engineering and drug discovery applications.There are currently no established methods for sorting pur populations of stem cell derived cardiomyocytes.  Methods that use fluorescent reporters require the introduction of a reporter vector and result in genetically modified cells, reducing their utility for clinical applications.  Other fluorescent-based staining methods have shown to be only applicable for selecting very mature cardiomyocytes.  Surface marker based methods require exposing human cells to products of animal origin, which may increase the risk of non-human pathogen transmission and render the cells unsuitable for clinical use.Second harmonic generation (SHG) is a laser-based technique that identifies stem cell derived cardiomyocytes based on the direct detection of myosin bundles, which generates a unique second harmonic signal when excited by intense laser pulses.  This signal is specific to the cardiomyocyte phenotype and is absent from undifferentiated stem cells and other non-cardiomyocyte cells that are found in the population following the directed differentiation of stem cells to the cardiac lineage.  SHG is able to discriminate cardionmyocytes at different stages of maturation/development, and can detect very immature cells.  When integrated into a flow cytometric configuration, non-invasive sorting for pure populations of stem cell derived cardiomyocytes is feasible. (more...)

The ability to capture and study circulating tumor cells is an emerging field with implications for early detection, diagnosis, determining prognosis, and monitoring of cancer, as well as for understanding the fundamental biology of metastasis. Current techniques of identifying and isolating such cells usually involve flowing cells in a chip across an antibody coated surface. However, these devices usually require complex geometries to ensure effective contact of the target cells with the functionalized surfaces. Such a problem can be avoided by using micro/nanoscale motors that can be programmed to scower an entire static sample as many times as needed. Further, the movement of the nano/microscale motor increases the solution convection thereby improving the diffusion of the target antigen, making for a quicker and more favorable recognition reaction. This also helps eliminate non-specific binding of the antigen while on its way to a clean environment for post-capture analysis. (more...)

Human skin is exposed to a multitude of chemicals on a daily basis, many of which can be hazardous or induce an irritant reaction.  While there is strict government regulation in regards to screening of these chemicals, this testing has typically relied on the use of animal models.  However, in recent years the use of in vitro screening methods has become more prominent, with reconstructed human epidermis models being a preferred technique.  Unfortunately, this approach is both time-comsuming and expensive, as well as being difficult to develop as a high throughput screen. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

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Researchers at the University of California, Irvine have developed a novel, non-invasive system to measure, quantify and analyze the spontaneous movements of infants in order to predict neurological disorders. The system involves capturing subtle movements of infants. This information is then analyzed and modeled by software. Movements identified may indicate that the infant has an increased risk for cerebral palsy, seizures, autism, intraventricular hemorrhage, cognitive delay or other neurological or motor conditions. By comparing to standards, the information may be used by a clinician to categorize the infant as either a high risk or low risk for the development of a neurological disorder. (more...)

The recent identification of rare cell populations within tissues that are associated with specific biological behaviors, for example, progenitor cells, has illuminated a limitation of current technologies to study such adherent cells directly from primary tissues. The micropallet array is a recently developed technology designed to address this limitation by virtue of its capacity to isolate and recover single adherent cells on individual micropallets. The capacity to apply this technology to primary tissues and cells with restricted growth characteristics, particularly adhesion requirements, is critically dependent on the capacity to generate functional extracellular matrix (ECM) coatings. The discontinuous nature of the micropallet array surface provides specific constraints on the processes for generating the desired ECM coatings that are necessary to achieve the full functional capacity of the micropallet array. We have developed strategies, reported herein, to generate functional coatings with various ECM protein components: fibronectin, EHS tumor basement membrane extract, collagen, and laminin-5; confirmed by evaluation for rapid cellular adherence of four dissimilar cell types: fibroblast, breast epithelial, pancreatic epithelial, and myeloma. These findings are important for the dissemination and expanded use of micropallet arrays and similar microtechnologies requiring the integrated use of ECM protein coatings to promote cellular adherence. (GunnN.M., MS; Bachman M., Li G.P., Nelson E.L.Fabrication and biological evaluation of uniform extracellular matrix coatings on discontinuous photolithography generated micropallet arrays. J Biomed Mater Res A. 2010 Nov;95(2):401-12.) (more...)

The field of the invention generally relates to methods of constructing high surface area structures using photoresist patterning in combination with electrochemical polymer deposition.The methods described herein can be used to create structures for a wide variety of applications including, but not limited to, micro-reactors, electrodes, and sensors (e.g., biosensors). (more...)

Researchers at the University of California, Irvine have developed a new controllable method to fabricate functionalized carbon nanowires that can then be covalently bound to antibodies, proteins, mRNA, DNA or other reagents. These antibodies and reagents may then bind with analytes of interest in solution causing a measurable change in the electrical current. Additionally, interdigitated electrode arrays may also be fabricated by using nanowires made from this method. (more...)

Electrochemical DNA biosensors are simple, inexpensive, and portable, making them attractive for decentralized genetic testing. Surface chemistry plays a major role in the overall performance of such biosensors. In particular, surface chemistry and coverage control is essential for assuring high reactivity, orientation/accessibility, and stability, while avoiding nonspecific adsorption and related background contributions. Several schemes for attaching nucleic acid probes to electrode surfaces and controlling the surface chemistry have thus been developed. Alkanethiol self-assembled monolayer (SAM) methods have been particularly useful for preparing reproducible probe-modified surfaces with high hybridization efficiency. Most often, two-component SAM monolayers of thiol-derivatized single-stranded oligonucleotide probe (thiolated capture probe, SHCP) and a short-chain 6-mercapto-1-hexanol (MCH) are used. Yet, such binary monolayers still suffer from background contributions and irreproducibility problems resulting from incomplete backfilling and surface defects. (more...)

Researchers at the University of California, Irvine have developed a Laplace pressure trap that can fuse droplets from different inlets and fuse droplets generated at different frequencies. The device traps and fuses droplets passively by balancing the driving hydrostatic pressure with increasing Laplace pressure imposed by the device’s design geometry. Above are video frames showing the Laplace pressure trap and of a single droplet fusion event at the Laplace trap. Frame A - Reference droplet can be seen waiting for its fusion partner. Excess partner droplets can be seen exiting towards the outlet. Frames B and C show the reference droplet and its fusion partner fuse and move toward the outlet. Frame D shows the next reference droplet approaching the trap. (more...)

Researchers at the University of California, Irvine have developed a device, system and associated software to automatically and objectively process and analyze a voice and report a score on the severity of the voice’s stutter on a real-time basis. (more...)

The Overman laboratory at the University of California, Irvine has generated a library of ~1,200 unusually diverse small drug-like molecules. (more...)

Researchers at the University of California, Irvine have developed a rotating gantry system that can be inserted and integrated into any magnetic resonance imaging (MRI) system to acquire images with a second modality (i.e. SPECT, PET, optical tomography, etc). (more...)

During their lifetime, some form of cancer affects more than 40 percent of the U.S. population. It is known that the catch-all term “cancer” includes a variety of diseases with varying etiology and prognoses. It is also known that the progression to metastasis radically changes treatment options. Despite the trend toward better understanding of the nuances of various types of cancer, the critical aspect of effective therapy remains early detection. An early indicator of cancer would allow physicians to proactively test and choose appropriate treatments, before disease progression has ruled out the most effective, early options. (more...)

It has been shown recently that in addition to their classical role in desensitizing G protein coupled receptors (GPCR’s), beta-arrestins can act as signaling molecules themselves. Thus, it is now widely held that GPCR’s are able to signal through parallel G-Protein and beta-arrestin pathways. Next generation GPCR therapeutics will be advanced by fine-tuning the actions along these pathways. GPCR ligands that preferentially activate the latter pathway are called beta-arrestin “biased” agonists. Different biological responses have been observed with such beta-arrestin biased agonists, compared with traditional GPCR therapeutics designed to activate G-proteins. (more...)

Determining oxygen levels in tumors is critical for advancing cancer diagnosis and therapy. A detailed knowledge of real-time changes in oxygen gradients within a tumor can assist in the profiling of tumor growth and improve the effectiveness of current treatment strategies, which function optimally at different oxygen concentrations. Small molecule luminescence has been suggested as a low cost, non-invasive alternative to traditional methods for sensing oxygen levels that are invasive, expensive, and/or lack sufficient spatio-temporal resolution to monitor real-time changes. In addition to sensing oxygen in tumors, luminescent small molecules, such as porphyrins, have been used for photodynamic therapy (PDT) to treat certain cancers by sensitizing oxygen for the production of cytotoxic reactive oxygen species (ROS). However, the utility of porphyrins has been hampered by low biocompatibility, lack of targetable delivery, and limited photophysical properties. The current invention describes a method for incorporating emissive porphyrins into proteins that offers a novel platform to enhance both oxygen sensing capabilities and targeted delivery to tumors. The bioluminescent proteins described not only have promising photophysical properties for biological use, but also are readily modifiable, biocompatible, and biostable. (more...)

This invention relates to the areas of the biochemical and chemical analysis of molecules in cells, and in particular to an assay and method for measuring the activation of internal chemical activity of a plurality of proteins in a single cell, a population of cells, or portion of a cell. The activity of multiple proteins in a single living cell, portion of a cell or in a group of cells is simultaneously measured by introducing reporter molecules into the cell(s) or a portion thereof, chemically modifying the reporter(s) by the enzyme of interest, terminating the modification reactions, removing the reporter(s) and modified reporter(s), and determining the amount of enzyme activity present by measuring or comparing the amount of reporter(s) and modified reporter(s) present. By performing a series of experiments at different time points, conditions, and varieties of cell types, a database is developed for molecular cellular mechanisms in health and disease states. By exposing cells to a variety of compounds data for drug development and screening is provided. (more...)

PTEN has been shown to be central in the regulation of cellular growth and survival. In many forms of cancer, mutations or loss of function in PTEN results in tumor formation - and as such PTEN is now appreciated as a central player in tumor suppression. Furthermore, PTEN has been shown to have a modulating role on cellular functions other than growth and survival, implicating this protein in diseases such as diabetes. Therefore, examination of PTEN in other models of disease may provide insight towards the understanding of mechanism and treatment of these diseases. (more...)

Tyrosine kinases (TKs) are a diverse family of highly regulated enzymes that, upon activation, phosphorylate target proteins on the amino acid tyrosine. TKs are involved in many cellular functions such as cell division and cell proliferation, as well as in several diseases including cancer and diabetes. Active site TK inhibitors, such as Imatinib (Gleevac) and Dasatinib (Sprycel), are the primary treatment options for chronic myelogenous leukemia (CML) and some other malignancies. Unfortunately, TK point mutations can prevent the inhibitors from binding and lead to drug resistance and disease relapse. Thus, an alternative method of inhibiting TKs would lead to treatment options for TK inhibitor-resistant patients and should reduce the rate of resistance to TK inhibitors in patients beginning therapy. (more...)

Classical neurotransmitters accumulate in the cytoplasm after both synthesis and reuptake from the synapse by the plasma membrane transporter. The neurotransmitters are then transported into and stored within vesicles for subsequent release. (more...)

The use of antibodies to target tumor cell-associated antigens for diagnostic and therapeutic purposes has been a critical step forward in cancer research. As protein engineering capabilities grow, researchers modify antibodies to alter inherent characteristics, such as affinity and immunogenicity, for enhanced imaging and tumor response. One example of this is in the conjugation of various radionuclides to small recombinant antibody fragments (i.e. diabodies and minibodies) for in vivo tumor cell targeting applications. However, it is not always advantageous to use radioactivity, and thus alternative detection systems are necessary. To that end, the search for high-sensitivity and high-specificity probes that circumvent the limitations of organic dyes and fluorescent proteins has led to the discovery and utilization of quantum dots, nanometer-sized semiconductor particles. Quantum dots are brighter than traditional chromophores, have greater stability, and can be used in multiplex imaging due to size-tunable emission wavelengths. To date, bioconjugates with quantum dots are coupled to intact antibodies whose large size makes it difficult to penetrate tissues and tumors. Therefore, it would be advantageous to monitor tumors with a robust, but small, bioconjugate for tandem in vivo monitoring and treatment. (more...)

Sophisticated systems in nature, such as cells, tissues, and organs in the human body, are capable of responding intelligently to external stimuli. Such sophisticated responses involve the complex interplay of multiple variables comprising external stimuli and internal factors. This interplay can involve synergistic and antagonistic relationship amongst multiple variables.Therefore, it is very difficult to manipulate a system, such as a group of cells or tissue, to behave in a desirable or optimal way without understanding the following: the effect each variable has on the system, the different possible states of each variable and how those states affect the overall system, and the relationship amongst the variables. A solution to this approach is to test all the combinations of the different stimuli and the different states of each stimulus by parallel tests. The number of test required increase exponentially with the number of stimuli. For example, the effectiveness of a six-drug combination cocktail on a tissue or cell line, which if only ten different concentration per drug is used, requires 106 or 1 million parallel tests in order to identify the optimal concentration. (more...)

According to the Polycystic Kidney Disease (PKD) Foundation, PKD is the most common genetic disease of the kidney. PKD affects 600,000 Americans and 12.5 million individuals in the world. Treatment for PKD, which includes dialysis or transplantation, is only available for kidney failure. (more...)

Researchers at the University of California Berkeley have developed a new substrate for use in diagnostic biomolecular/protease testing, both in point-of-care and in clinical diagnostic lab setting. The technology provides an advance upon current colorimetric and flourometric hydrolytic activity assays, eliminating sensitive measurement equipment e.g. ELISA. Protease deviation from homeostatic behavior has been correlated to disease states e.g. rheumatoid arthritis, atherosclerosis, Alzheimer’s, stroke and cancer. This substrate holds the potential to revolutionize passive diagnostic tests such as pregnancy test and HIV lateral flow assays, in addition to advancing current hydrolysis assay technology. The substrate may provide for detection outside the biological world e.g. cocaine and lead. The substrate provides for a low-cost, portable tool that could expand the current testing capabilities of point-of-care diagnostic into protease activity monitoring. A hand held apparatus supporting the basic invention is thus also proposed to provide for a complete and ready to use innovation. (more...)

Background: Prostate cancer, alopecia, hepatocellular carcinoma, and acne vulgaris are a few examples of the myriad of diseases linked to androgen receptor signaling. These diseases have a significant impact on human health; for example, The American Cancer Society estimates that in 2009, prostate cancer will cause 27,360 deaths and 192,280 new cases will be diagnosed. In fact, one man in six will get prostate cancer in his lifetime and one in thirty-five will die from this disease. Androgen receptor inhibitors are the primary treatment option for androgen-related diseases. Current inhibitors prevent ligand binding to the androgen receptor, but these treatments can result in acquired resistance and serious side effects. Due to the limitations of current treatment options, alternative antiandrogen therapies are urgently needed. Inventions: Prominent UCSF scientists have discovered a suite of novel small molecule inhibitors of the androgen receptor. Using an innovative approach to avoid the pitfalls associated with current antiandrogen therapies, Dr Diamond’s team identified multiple compounds that inhibit the androgen receptor post-ligand binding. The team validated this work by demonstrating the ability of these compounds to inhibit endogenous androgen receptor activity in prostate cancer-derived cell lines. Further validation in animal models of prostate cancer is underway for many of the novel compounds. Significantly, the team demonstrated that one such compound, pyrvinium pamoate, inhibits androgen receptor signaling in vivo and induces prostate atrophy. Furthermore, pyrvinium synergizes with known inhibitors that prevent ligand binding (Jones et al. 2009). In addition to the novel compounds, an assay to detect selective gene regulation by ligand dependent transcription factors has been developed. This assay could be used to uncover additional candidates for androgen receptor inhibition. The assay has been successfully tested on the glucocorticoid receptor and led to the discovery of selective modulators of this receptor for treatment of inflammation, allergic, and immune-mediated diseases.  Three patents have been filed on these technologies to provide a strong IP position for a licensee. (more...)

The present invention relates to a method for determining cancer susceptibility by quantifying DNA damage-induced mRNA in whole blood. (more...)

BACKGROUND:  Patients with certain types of tumors, in particular brain tumors, will frequently rely on radiologic imaging, such as magnetic resonance imaging (MRI), for diagnosis and treatment monitoring. Unfortunately, MRI and similar modalities are often subject to interpretation and can be highly subjective in nature, making it difficult to differentiate between actual tumor recurrence and treatment effect. Subsequent or alternate methodology involving biopsy or other surgical procedures, can be highly invasive, dangerous, and lead to an extensive recovery time in patients undergoing such procedures. A less invasive method to reliably identify tumor recurrence would be valuable to clinicians and their patients during evaluations following treatment and/or surgical resection of a tumor.   TECHNOLOGY:   UCSF inventors have discovered a novel cancer biomarker that is expressed on the surfaces of myeloid cells, so that tumors can be evaluated for recurrence by screening small amounts of peripheral blood in patients. So far, these findings have been done in glioblastoma and prostate cancer patients, but further studies are underway for other types of solid tumors. (more...)

Causes of blood cell diseases range from genetic, as in myeloproliferative disorders (MPDs) and cancer, to infectious, as in malaria. In all cases, treatments are directed at modulating the survival or differentiation of the affected cell population. Unfortunately, drug and vaccine development are continuously hampered by the absence of good, in vivo models that can mimic the complexity of the human immune system. (more...)

Presently, there are no biological tests to aid in the diagnosis of psychiatric disorders. Therefore, the diagnosis is, largely based on behavior rather than underlying biology or pathophysiology. Accurate diagnosis frequently requires years for the longitudinal course of symptoms to be clear. Current behavior-based diagnoses have a limited ability in predicting a course or response to treatment. A genetic test for detection of pathogenic mutations in the genome will enable a more rapid and accurate diagnosis of the disorder, thereby leading to better treatment. No such test exists and there is currently only a limited understanding of the biological mechanisms of most psychiatric disorders. (more...)

The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes to monitor disease progression or treatment efficacy of candidate drugs. (more...)

The present invention relates to compositions of a member of the cholesterol-dependent cytolysin (CDC) family and methods of using these compositions to activate toll-like receptor 4 and to identify modulators of toll-like receptor 4 activation. Activation of toll-like receptor 4 by endotoxin or lipopolysaccharide (LPS) can lead to septic shock or septicemia. Compounds identified as modulators, and more particularly inhibitors, of toll-like receptor 4 activation by a member of the CDC family are expected to be useful in the treatment of septic shock and/or septicemia. It is believed that isolated CDCs, fragments, or mimetics may inhibit the interaction of toll-like receptor 4 and endotoxin or LPS. (more...)

Neurons in the brain communicate with other neurons, or with non-neuronal cells, by sending or sensing neurotransmitters or neuromodulators. The development of methods to measure the amount of neurotransmitters and neuromodulators in vivo in the brain is critical in order to study the large number of pathologies associated with abnormal levels of extracellular signaling molecules. In vivo monitoring of biochemical compounds is presently performed by microdialysis methods or by direct electrochemical measurement in situ. The main drawback of microdialysis is its temporal resolution, which can be several orders of magnitude lower than the time scale of brain cell electrical activity. Direct in vivo electrochemical methods display a lack of chemical sensitivity. Neither of these techniques is capable of measuring two compounds simultaneously and unambiguously. (more...)

UCSF scientists have identified novel compounds to treat glaucoma. Specifically, topical or intraocular application of synthetic thyroid hormones increases aqueous outflow. Scientists have uncovered the direct biochemical mechanism by which synthetic thyroid hormones may reduce IOP. Based upon this knowledge, they have developed methods to screen for novel therapeutic drugs that target this pathway and lower IOP in glaucoma patients. (more...)

William Santo with prominent University of California researchers Francisco Ramos-Gomez, DDS, MS and Stuart Gansky, DrPH, has developed a software package that allows dental researchers to enter participant examination data electronically for the primary purpose of analyzing disease outcome measures related to caries, plaque, and periodontal measures for clinical research. Designed from the ground up by dental experts to meet the specific needs of research-oriented dentists, the software may be used in either a real-time capacity during an examination or for post-examination transcription from original paper, digital imaging, or other sources. This HIPAA-compliant package is extremely stable, flexible, customizable, and easy to use, even by those with little prior dental subject knowledge. (more...)

Gene therapy via viral vector technology has been associated with dangerous complications and risks. UCSF investigators have discovered a process that permits defective genetic sequences to be replaced with greater efficiency and potentially fewer side effects. The process, small fragment homologous replacement (SFHR), allows genes to be repaired in a site specific fashion and does not require the insertion of new genetic material into the genome. Thus, the SFHR approach should be applicable to a wide variety of gene therapy applications requiring the repair of specific mutations in DNA sequence. Furthermore, assay methods have been developed to monitor and quantify gene targeting frequency and to differentiate between cells carrying modified and unmodified DNA. (more...)

BACKGROUND: In recent years, there has been a dramatic increase in the incidence of diabetes worldwide. According to the International Diabetes Foundation, about 246 million people worldwide have diabetes and this number is expected to increase to 380 million by 2025. Type 2 diabetes accounts for about 90% of all cases. The current gold standard for diagnosing diabetes is a test for elevated blood sugar level following an overnight fast. Another test frequently used is the oral glucose tolerance test. However, these tests based on blood glucose can overlook approximately 25% of people who will develop type 2 diabetes, yet have normal blood glucose levels several years before diagnosis. Just in the US alone, 57 million people have pre-diabetes with blood glucose levels that are higher than normal but not high enough to be classified as diabetes. Recent research has shown that some long-term damage to the body, especially the heart and circulatory system, may already be occurring during pre-diabetes. Therefore, there is a need for assays to detect risk for type 2 diabetes a) prior to the onset of pre-diabetes as well as b) in individuals who have normal blood glucose levels. DESCRIPTION: Researchers at UCSF in collaboration with researchers at the University of Catanzaro have discovered mutations in a nuclear regulatory gene that are predictive of type 2 diabetes. The gene encodes a transcription factor necessary for cells to make insulin receptor, and low levels of insulin receptor lead to insulin resistance and type 2 diabetes. Researchers sequenced genomic samples from 3000 type 2 diabetes patients and 2000 sex and age matched non-diabetic controls. These mutations were observed in 10% of type 2 diabetes patients, while mutations were observed in less than half a percent of control patients. Since these mutations were 20-fold lower in controls, a robust diagnostic with high positive predictive value can be developed. Such a gene-based approach to assessing susceptibility to type 2 diabetes provides a more definitive diagnosis than todays diagnostics, allowing physicians to change patient care. Furthermore, genetic tests are accurate as early as infancy, when diet and exercise habits are being formed. (more...)

Researchers at the University of California have developed a fiber-based spectroscopic technique that can be used to quantify optical properties in superficial layers of tissue. (more...)

As the development of protein products and peptide mimetics becomes more prevalent in the biotechnology and pharmaceutical industries, the ability to mimic the protective and modulate the inflammatory effects of the recognition protein of the classical complement cascade in blood and body fluids will increase. (more...)

Jaagsiekte sheep retrovirus (JSRV) causes broncheolo-alveolar carcinoma in sheep and is a significant veterinary problem world-wide. Clinically and histopathologically, this disease has strong resemblance to broncheolo-alveolar carcinoma (BAC) in humans which accounts for approximately 25% of human lung cancers. (more...)

Thrombin is an enzyme in the blood that plays a key role in platelet formation during injury. While blood coagulation is essential for a surface wound, platelet activation underlies various pathological situations such as unstable angina pectoris, myocardial infarction and stroke. Thrombin is mediated by protease activated receptor-1 (PAR-1) which is expressed in the nervous system and in platelets. Once activated by thrombin, PAR-1 induces rapid and dramatic changes in cell morphology that is controlled by a series of localized ATP-dependent reactions. (more...)

Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction. (more...)

University of California, Irvine researchers have developed a novel transgenic mouse model that contains the three major genes that contribute to the hallmark pathological features of Alzheimer's disease. These mice are exceedingly valuable for therapeutic investigations and for basic research aimed at understanding the behavioral, physiological, molecular/cell biological, and pharmacological processes leading to dementia in an animal model. Even though these mice contain three transgenes, the mice essentially breed as readily as a "single" transgenic line, greatly facilitating the establishment and maintenance of an animal colony. (more...)

In many disciplines, quantitative measurements of color are required to evaluate nondestructively the state of an object (e.g., quality of produce). This characterization is typically performed using contact point measurement devices. A limitation of these devices is that multiple measurements are required to characterize an entire object; if multiple objects must be characterized, then this process may be time consuming. Furthermore, these devices interrogate both superficial and deeper structures in the object, and do not possess the ability to discriminate between these structures. (more...)

Patent "WO02/31145" discloses a newly deorphanized GPCR system, Neuropeptide S (NPS), the endogenous ligand, and its cognate GPCR. However this patent does not detail the pharmacological or physiological function of NPS and its GPCR. University of California, Irvine researchers have characterized NPS's function in the CNS. (more...)

Antioxidant and xenobiotic metabolizing enzymes are critical in the protection against chemically induced oxidative/electrophilic stress in cells that cause damage, DNA mutation, apoptosis, and cancer. Transcription of these cytoprotective genes and xenobiotic metabolizing genes is regulated through cis-active sequences known as antioxidant response elements (ARE). Coordinated induction of these genes mediated through the ARE is regulated by a signal transduction system that is still in the process of being fully characterized. Regulation of ARE function is mediated by various basic leucine zipper transcription factors including members of the 'cap n collar' (CNC-bZIP) Nrf1 is a CNC-bZIP protein that regulates the expression of ARE. Previous attempts at developing viable Nrf1 deficient mice were unsuccessful since the Nrf1 gene is necessary for embryonic development. (more...)

Preservation of posttranslational modifications during purification is crucial for successful mass spectrometric analyses of protein modifications. Current tandem-affinity purification strategies require native conditions and are therefore susceptible to loss of posttranslational modifications during cell lysis and purification because modifying as well as de-modifying enzymes remain active under these conditions. (more...)

The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis. EF-Tu also binds other ligands, including four structurally distinct families of antibiotics. The lack of sequence homology among the identified EF-Tu ligands demonstate promiscuous peptide binding by EF-Tu. (more...)

Sodium/potassium ATPases (Na+/K+-ATPases), a family of multi-subunit ion pumps, are the most important active transporters in animal cells. They are required for maintaining the electrochemical gradient responsible for resting membrane potentials in neuronal cells and for the function of other transport proteins in a variety of cell types. The important regulatory activities of Na+/K+-ATPases make them an attractive therapeutic target for the treatment of neurodegenerative, cardiac, and other diseases. To date, there are unmet medical needs for the treatment of these diseases, and it is desirable to discover and develop novel therapeutic agents aimed at treating ion pump related disorders. (more...)

The determinant factor for the successful applications of delivering drugs is to develop a non-viral and efficient carrier. Cationic lipid based liposomal carriers are the most attractive non-viral solution. Advantages of liposomal vectors include safety, lack of immunogenicity, ability to package large DNA molecules and ease of preparation. However, the conventional processes for catatonic lipids and DNA complex formulation are normally irreproducible. (more...)

Sjogren's Syndrome is a grave autoimmune disease in which destruction of the exocrine glands leads to severe dryness of the eyes and mouth, with additional systemic complications. The pathogenesis of Sjogren's Syndrome is unclear, and treatment options are limited. Development of good animal models of the disease might lead to effective treatments for human patients, as well as a greater understanding of the cellular and molecular alterations that underlie disease progression. (more...)

Prokineticin 2 (PK2) is a signaling molecule that is critical for transmitting circadian rhythms from the suprachiasmatic nucleus, the master pacemaker that drives circadian rhythms in animals. It is known that disrupted circadian rhythms are strictly associated with many mood disorders, such as bipolar disorders, depression, and seasonal affective disorder. The functional role of PK2 in anxiety and depression-like behaviors was investigated and provide a new therapeutic target and system for the discovery of treatments for mood disorders and stress. (more...)

An epidemic of metabolic diseases including type 2 diabetes and obesity is undermining the health of people living in industrialized societies. There is an urgent need to develop innovative therapeutics. (more...)

Affordable point-of-care diagnostics (POC-Dx) devices are critical in the developing world to ensure the efficient use of limited medical resources as well as the rapid surveillance of emerging diseases.  Current diagnostic techniques often lack sensitivity, speed and portability.  To address these limitations, Researchers at UC Berkeley have designed a robust and versatile microfluidic system for inexpensive, rapid POC-Dx.  The design employs RNA riboswitches immobilized in a microfluidic chip for molecular detection and subsequent signal reporting.  Riboswitches can be systematically engineered to become activated upon binding with a specific target of interest, including proteins, sugars, and small metabolites.  This activation allows for in vitro translation (IVT) of a reporter protein that can be readily detected with no additional optical equipment.  The assay is conducted in a microfluidic chip to enhance portability and speed, taking advantage of micro-scale dynamics. (more...)

Mycobacteria are a significant cause of morbidity and mortality, particularly among immunocompromised or elderly individuals and in countries with limited medical resources. Ninety-five percent of human infections are caused by seven species: Mycobacterium tuberculosis, M. avium (also known as the mycobacterium avium complex or M. avium-intracellulare), M. leprae, M. kansasii, M. fortuitum, M. chelonae, and M. absecessus. The most common mycobacterial infections in the United States are pulmonary infections by M. tuberculosis or M. avium. Such mycobacterial infections have been of increasing concern over the past decade, particularly in light of the increasing incidence of multi-drug resistant strains.   Mycobacterium tuberculosis is the causative agent of the disease tuberculosis in humans. Estimates indicate that one-third of the world's population, including 10 million in the U.S., are infected with M. tuberculosis, with 8 million new cases and 3 million deaths reported world wide each year. Although incidence of tuberculosis steadily decreased since the early 1900s, this trend changed in 1984 with increased immigration from endemic countries and increased infection among homeless individuals, drug and alcohol abusers, prisoners, and HIV-infected individuals. The increasing occurrence of drug-resistant strains requires continued research into new and more effective treatments. SUMMARY OF THE INVENTION Novel mycobacterial sulfation pathway proteins and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway protein. The present invention further provides genetically modified mycobacteria having a defect in a sulfation pathway enzyme gene; and immunogenic compositions that include such genetically modified mycobacteria. ABSTRACT Novel mycobacterial sulfation pathway enzymes and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway enzyme. Normal.dotm 0 0 1 85 489 UC Berkeley 4 1 600 12.0 0 false 18 pt 18 pt 0 0 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} (more...)