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Human Systems

Latest Innovations
A DNA-Based Diagnostic Test for the Identification of Individuals having the Mutation causing the Ectodermal Dysplasia (ED) Genetic Defect in Sheep Researchers from the University of Illinois have identified a new inhibitor of the androgen receptor (AR), CPIC, that would be effective in the treatment of... Read More Researchers from the University of Illinois have identified a new inhibitor of the androgen receptor (AR), CPIC, that would be effective in the treatment of Castration Resistant Prostate Cancer (CRPC). CPIC targets a novel site on the full-length and truncated forms of the AR, present in the CRPC. Initial in vivo data has demonstrated that this new class of compounds is capable of inhibiting growth of prostate cancer cells. Furthermore, CPIC has shown to be 40x more potent against the truncated AR compared to current small molecules against the truncated AR.
Biosynthesis of Lantibiotics: In vitro semi-synthetic production methods for generation of industrial antibiotic, Lacticin 481 This invention allows the engineering of semi-synthetic lantibiotics to a much larger extent than using typically practiced in vivo methods. The method is the... Read More This invention allows the engineering of semi-synthetic lantibiotics to a much larger extent than using typically practiced in vivo methods. The method is the first in vitro reconstruction lantibiotic photosynthesis and introduces non-proteinogenic amino acids. Lantibiotics are peptide-based compounds produced by bacteria that live on lactic acid. They are used as natural antibiotic food preservatives as an alternative to chemical reagents and have been used for half a century without any significant signs of lantibiotic-resistant bacteria popping up. Researchers at the University of Illinois have isolated and purified the LctM enzyme, responsible for synthesis of lacticin 481. This approach, the first in vitro reconstruction of lantibiotic biosynthesis, allows for lantibiotic engineering and opens the door to possible generations of new lantibiotics with greatly increased yields and improved activities. Applications Food preservation Industrial enzyme production Bioengineering of novel lantibiotics Benefits Greater Production Flexibility: In vitro methodology allows for lacticin 481 production using semi-synthetic substrates. Avoids Complications of In Vivo Production: In vitro methods avoid product cytotoxicity, degradation and bypasses many of the In vivo regualtory complications. Better Resistance Profile: Lantibiotics have been used for half a century in more than 40 countries without any significant signs of lantibiotic-resistant bacteria appearing. More Possibilities: The method works well with combinatorial techniques, increasing the number of substrates that can be used in production of lacticin 481. In addition, isolation of the LctM enzyme allows for more efficient synthesis with greater structural and functional tolerance of the biosynthetic pathway.
Ionizable Isotopic Labeling Reagents for Relative Quantification Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with... Read More Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with biological samples. This invention provides ionizable, isotopic labeling reagents and labeling reaction products, answering the current need for relative quantification using mass spectrometry. Absolute quantification of an analyte relies upon the addition of an internal standard differing only in its isotopic form. However, it is impractical to add an isotopic standard for every compound when performing more comprehensive metabolic profiling. Relative quantification between samples is more amenable to analyzing broad classes of compounds, and it often provides very useful biological information. Heavy and light isotopic forms of methylacetimidate have been synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine have also been synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as these found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional liquid chromatography mass spectrometry (LC/MS) applications. This invention improves the precision of relative quantification by minimizing or negating errors associated with run-to-run irreproducibility. Such errors can arise from variations in mass spectrometric detection sensitivity, such as those caused by ionization suppression in electrospray, or from retention time differences between runs. The isotopic pair of labeled compounds co-elute within a single run. Therefore, they have identical retention times and are electrosprayed from identical solution conditions.
Gene Cluster Capable of Enabling the Biosynthesis of the Antimicrobial Compound, Rhizocticin In Bacillus subtilis Phosphonic and phosphinic acids are bioreactive compounds that have been used as antibiotics, antifungal agents, antimalarial drugs, and herbicides. Rhizocticins... Read More Phosphonic and phosphinic acids are bioreactive compounds that have been used as antibiotics, antifungal agents, antimalarial drugs, and herbicides. Rhizocticins are naturally occurring phosphonates produced by Bacillus subtilus that have antifungal properties and interfere with the biosynthesis of the amino acid threonine. By varying the N-terminal amino acid group in the rhizocticin compound, it is possible to alter its biological activity. In particular, oligopeptides that are created by varying this amino acid could potentially allow enhanced capability for controlling selectivity for targeting particular organisms. As a result, compounds are less toxic to the host species and hold more promise for creating therapeutics. Despite the potential for making these types of compounds, organic synthesis has never been achieved due largely in part to the fact that the biosynthetic pathway has not been well understood. University of Illinois scientists have now identified the gene cluster responsible for biosynthesis of rhizocticin in B. subtilis, making biosynthesis of rhizocticin compounds possible. Details Original attempts to isolate and identify this unquie cluster failed, however, the genome of a specific strain of B. subtilis was sequenced and open reading frame locations were determined and annotated. Upon comparison with a non-rhizocticin-producing strain of B. subtilis, the rhizocticin biosynthetic gene cluster was able to be identified and isolated. There are more than 10 genes in the B. subtilis rhizocticin cluster. The biosynthetic pathway was proposed using sequence homology (similarity) for each of the genes. One particular gene in the cluster was identified by the inventors as being unique to this biosynthetic pathway. The cluster responsible for rhizocticin was verified by successfully inserting it into a non-producing strain of B. subtilis. Applications Pharmaceutical industry: Synthesis of biologically active compounds and analogs of rhizocticin. Production of novel oligopeptides with therapeutic properties Agricultural industry: Herbicide Benefits The identification of specific gene cluster for biosynthesis of rhizocticin allows: Specific synthesis of compounds; Control of biological activity of compounds; and Control of compound toxicity in mammals
Compounds That Selectively Induce Cancerous Cell Death in the G1 Phase of the Cell Cycle Malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients is 6 months. This coupled with the... Read More Malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients is 6 months. This coupled with the alarming rise in incidence of melanoma (46,170 cases of in situ melanoma are expected to be newly diagnosed in 2005) warrants research into novel means to treat melanoma. Through the synthesis of a combinatorial library of potential proapoptotic agents, a novel class of small molecules (triphenylmethylamides, TPMAs) have been identified that are effective agents in killing melanoma cells, as well as other cancer cells. The majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. In contrast, these TPMAs, act in the G1 phase of the cell cycle. Many of the TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 of 0.5 ?M), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs dramatically reduce the level of active nuclear factor ?-B (NF?B) in the cell; NF?B is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. With regard to status of development, multiple generations of compounds have been tested and have shown efficacy with primary melanocytes, while these same compounds have shown to be largely non-toxic in initial rodent studies assessing changes in body weight and death. In addition, the National Cancer Institute?s 60-cell line screen has demonstrated activity of the compounds against a broad range of cancer types. Additional detailed information about this technology can be found in the recently published article: Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest (JACS 2005, 127, 8686-8696) Applications Chemotherapeutic treatment of Melanoma Chemotherapeutic treatment against other cancers, such as breast, colon, non-small cell lung carcinoma (NSCLC), etc. As a research reagent that arrests cells in G1. Benefits Potent death inducers in melanoma cell lines with potencies in the 0.5 - 1.0 M range Markedly less (8-12-fold) toxicity to the non-cancerous human bone marrow cells National Cancer Institute's 60-cell line screen demonstrated the compounds are quite active against a broad spectrum of cancers and confirmed the IC50 value of 600 nM against the UACC-62 melanoma cell line Initial animal testing suggests that mice can tolerate concentrations as high as 200 mg/kg Efficacy and water solubility are being increased as additional chemical modifications are made with later generation compounds
Compounds for the Treatment of Fluoquinolone resistant infections Researchers from the University of Illinois have synthesized a variety of compounds with strong activity toward fluoroquinolone resistant bacteria. These compounds... Read More Researchers from the University of Illinois have synthesized a variety of compounds with strong activity toward fluoroquinolone resistant bacteria. These compounds not only combat resistant bacteria, but also reverse the resistance making it possible to again treat with the common fluoroquinolone drugs.
Supramolecular Assembly for Non-Viral Gene Delivery Gene therapy is an approach for human disease treatment. This is done by inserting nucleic acids into cells to produce proteins, fix or replace damaged genes, and... Read More Gene therapy is an approach for human disease treatment. This is done by inserting nucleic acids into cells to produce proteins, fix or replace damaged genes, and inhibit expression of harmful genes. The gene delivery systems are classified into viral and nonviral systems. There are several advantages in nonviral delivery systems, including biological safety (safer than viral vehicle), low immunogenicity, ability to deliver large genes, and large scale production at a reasonable cost. However, non-viral delivery systems have barriers that need to be overcome such as: biocompatibility of polymers used (toxicity) transfection efficiency, nuclear localization, and packaging and unpackaging of DNA. This invention addresses some of these issues. This technology uses a multi-component approach to gene delivery that allows DNA binding strength, endosomolytic capabilities and targeting to be tuned separately in the resulting vector. Applications Pharmaceutical industry Gene delivery/therapy companies Research Reagents Companies selling research reagents Benefits Better transfection efficiency compared to other gene therapy delivery systems Easier: Does not require chemical reactions to assemble the supramolecule Able to arrive at a useful delivery vehicle using combination at a faster rate.
DNA Sequencing Systems Using Nanoscale Field Effect Sensor Arrays This invention is a novel approach to performing DNA sequencing-by-synthesis methodology that is anticipated to make DNA sequencing routine, highly accurate and... Read More This invention is a novel approach to performing DNA sequencing-by-synthesis methodology that is anticipated to make DNA sequencing routine, highly accurate and affordable. The approach is a silicon-based field effect nanoscale sensor array using a sequence-by-synthesis methodology. PCR is performed locally in each pixel through the use of recently developed methods for heating fluid using a silicon field effect sensor, and then the amplified molecules in the pixel are detected in a label-free electrical manner where the added charge during the synthesis process is detected using the same thin-film SOI transistor. Cost is significantly reduced since the nucleotides do not need a fluorescent label, there is no need for gel electrophoresis, and the entire machinery of optical signal processing is unnecessary. In addition, since the silicon field effect sensors when used in a nanoscale dimension can be very sensitive and detect the charge from just a few molecules, it is quite feasible that the PCR amplification can be utilized with very few cycles. Reduction of PCR cycling would reduce the usage of costly reagents. The information retrieval can be scaled and the information obtained per unit time is maximized.
Microfluidic Device for the Preparation of Highly Viscous, Non-Newtonian Mixtures with Application to In-Meso Membrane Protein Crystallization Devices for mixing of significantly different fluids: Applications in protein crystallization. A microfluidic device for preparing a mixture, has... Read More Devices for mixing of significantly different fluids: Applications in protein crystallization. A microfluidic device for preparing a mixture, has a mixer. The mixer includes a plurality of chambers, each chamber having a volume of at most 1 microliter, a first plurality of channels, each channel fluidly connecting 2 chambers, a plurality of chamber valves, each chamber valve controlling fluid flow out of one of the plurality of chambers, and a first plurality of channel valves, each channel valve controlling fluid flow through one of the first plurality of channels. This device enables the metering and mixing of two fluids of significantly different viscosities and potentially non-Newtonian fluid behavior. Mixing is performed using large pneumatically acuated valves to drive fluid flow in a sequence that prevents fluid stagnation and facilitates mixing. The device can be used, for example, in the preparation of aqueous/lipid mesophases for in-meso membrane protein crystallization.
Three-Dimensional Nonlinear Interferometric Vibrational Imaging of Molecules Nonlinear Interferometric Vibrational Imaging (NIVI) NIVI offers unmatched capabilities in biomedical imaging by performing non-invasive three-dimensional molecular... Read More Nonlinear Interferometric Vibrational Imaging (NIVI) NIVI offers unmatched capabilities in biomedical imaging by performing non-invasive three-dimensional molecular imaging of living specimens and tissue. This imaging platform interferometrically detects nonlinear optical signals based on the vibrational states of atomic bonds within target molecules and may be used for diagnostics and for delivery of focused ablative treatment. Developed as part of a portfolio of optical contrast agents and molecular detection technologies that enhance the ability of optical coherence tomography (OCT) to non-invasively map molecules in living specimens and diagnose disease where it starts. OCT utilizes low-coherence interferometry to measure the intensity of reflected or backscattered light to form images with micrometer resolution, is readily integrated with existing optical instrumentation and has application across a wide range of biological, medical, surgical, and non-biological specialties. Benefits: Images a range of molecular species simultaneously with a single instrument Requires no exogenous labels to detect specific molecules Permits precise density determination without background signals Allows 3-D discrimination of molecular density and enhancement Provides 2D and 3D imaging of biological tissues, showing both molecular information and structural information. These measurements could provide clinical diagnostic value without requiring a biopsy. These innovations offer better sensitivity, better false signal rejection, and more flexibility than CARS microscopes, and can potentially be much cheaper and easier to operate. A set of CARS (Coherent Anti-stokes Raman Spectroscopy) related inventions that efficiently enable in vivo three-dimensional imaging of biological tissues without added stains or markers. The features examined are actually the density of molecules in tissue with particular molecular ro-vibrational features. This is a major improvement over NIVI (Non-linear Interferometric Vibrational Imaging). Determination of both structural and chemical attributes of biological tissues either as biopsy or in vivo. Laboratory set-ups exist, many animal and human tissues have been imaged. Ready for product development engineering to: reduce cost, provide customer-centric packaging, documentation, regulatory compliance, etc.

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