Welcome to BioCAT

The APS is shutting down on April 17, 2023 for an upgrade. During the APS-U dark period the BioCAT beamline will be unavailable for x-ray experiments. We anticipate resuming user experiments in summer/fall of 2024.

Find out more about: the APS-U; SAXS experiments during the APS-U dark period; Fiber experiments during the APS-U dark period.

Science Highlights

Understanding Phase Separation Could Impact Treatment of Neurodegenerative Disease

Living cells are amazing little biochemical factories that conduct countless chemical reactions in a cellular soup packed with lipids, proteins, nucleic acids, and ions, keeping them all in their proper places at any given time. Cells maintain this organization even while carrying out complex tasks such as cell division, signaling, transcriptional regulation, and stress responses. One example of this is the careful management of stress granule formation, a process in which membraneless organelles transiently form to control the utilization of mRNA during stress. These granules form and disperse through reversible liquid-liquid phase transitions involving proteins and RNA in the granules. Recent research has demonstrated that RNA-binding proteins in these granules contain intrinsically disordered sequences, called prion-like low-complexity domains (PLCDs), that are critical to regulation of these reversible phase transitions. There is also mounting evidence that these transitions may be disrupted in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), in which mutations in PLCD-containing proteins, such as hnRNPA1, have been implicated as a cause of the disease. Recent work that relied on data from BioCAT, and published in the journal Nature Chemistry aimed to learn more about how these phase transitions are regulated. These findings will provide important information about the causes of diseases like ALS.

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Targeting Cancer at the Level of DNA Expression

The last 20 years have brought a revolution in targeted therapies for cancer. Small-molecule inhibitors and monoclonal antibodies that target a specific aberrant protein in tumors have provided cancer patients with treatments that are associated with fewer side effects and longer survival than conventional chemotherapy. This has been, in large part, the result of intensive research into the role of oncogenes in cancer development. Oncogenes are normal cellular genes that have become mutated in such a way that they aberrantly promote the uncontrolled cell growth seen in cancer. They are often proteins involved in growth control or activation of cellular signaling; inhibiting these mutated proteins has proven to be effective in stopping the growth of many cancers. Research by a team from the Brown Cancer Center at the University of Louisville in Kentucky using BioCAT and published in the journal Nucleic Acids Research promises to extend these treatment possibilities to control these oncogenes at the gene expression level. The work, based on the discovery that DNA in the promoter region of many genes forms higher order structures that could provide unique druggable targets for intervention, extends structural knowledge of the promoter regions of three important oncogenes.

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Understanding the Structural Implications of Genetic Mutations in Heart-Muscle Disease

Cardiomyopathies are diseases of the heart muscle in which the muscle of the pumping chamber (ventricle) can become enlarged (dilated cardiomyopathy; DCM) or thickened (hypertrophic cardiomyopathy; HCM), potentially leading to heart failure. There are currently no effective treatments but the disease often has a genetic component related to mutations in the heart muscle proteins that are involved in muscle contraction, so some researchers have focused their therapeutic development efforts on correcting these muscle contraction problems based on the structural basis of the defect. A recent study from a team of researchers using BioCAT employed humanized mouse models expressing mutations observed in patients with HCM and DCM to evaluate the structure-function relationships and the changes observed in cardiac muscle contraction with these mutations. The work, published in the Proceedings of the National Academy of Sciences of the United States of America, provides a deeper understanding of the effects of cardiomyopathy-causing gene mutations on heart muscle contraction that could lead to the development of new therapies for this potentially life-threatening disease.

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News

BioCAT Plans for the APS-U Dark Period

The APS will shut down on April 17, 2023 for a major year-long upgrade, the “APS-U” project. There will be no user access to the APS during this “dark period”. The APS plans to restart operations at the beginning of April, 2024, followed by several months of safety and technical commissioning at all beamlines. We anticipate that BioCAT will be unavailable for experiments from the end of April 2023 until early summer 2024. During this ~14 month shutdown, we plan to help support experiments by our users at other beamlines, including sending BioCAT staff to other beamlines to help with some of the more complicated experiments.

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MuscleX 3 wrapup

BioCAT offered its third MuscleX workshop entitled “Sarcomeric regulation mechanisms in health and disease” from May 18 -19 2023. This entirely virtual workshop had 200 registered attendees.

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Everything BioSAXS 9 Wrap-up

BioCAT held its ninth intensive HOW-TO course in BioSAXS from 2/28/22-3/3/23 with 32 remote participants. There were four days of lectures and hands-on software tutorials on the basics of BioSAXS data collection and processing from expert practitioners in the field. Participants could elect to mail in samples for data collection prior to the course, and roughly half of them sent research samples and were able to analyze their own data as part of the workshop.

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