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Welcome to the YWHAG Research Hub where we bring together scientists, clinicians and industry leaders to drive progress towards a cure for conditions associated with the YWHAG genetic mutation. In this dedicated space, we showcase current cutting-edge research in the field and unravel the complexities of the YWHAG gene.
Our goal is not just to advance our understanding– but to translate this knowledge into tangible treatments. By fostering a synergistic environment, we aim to accelerate research, encourage innovative therapies, and facilitate the exchange of ideas and discoveries.
This section serves as a collective hub of progress to highlight significant strides as we journey together towards a cure. Join us in this endeavor as we push the boundaries of science and medicine to transform the lives of those affected by YWHAG-related conditions and beyond.
University of Leicester
A small team is currently focused on developing plasmids necessary for expressing mutant variants. They anticipate having the protein ready by early 2024, which marks a significant milestone in our project. Once they have the protein, the next step will involve conducting binding studies. These studies are crucial as they will allow us to understand how the mutations in the 14-3-3 gamma protein affect its interaction with partner proteins. This research is not only pivotal in advancing our knowledge of the protein's function but also in exploring potential therapeutic targets for conditions associated with its mutations.
Rare Base
Rare Base’s drug repurposing is centered on identifying existing medications that can be effectively redirected to treat rare genetic disorders. The goal is to leverage the pharmacological properties of already approved drugs, which have known safety profiles, to expedite the treatment process for rare diseases. This approach aims to reduce the time and cost associated with drug development, offering a more immediate therapeutic option for patients with rare conditions. The proposal involves extensive research to understand the molecular and genetic underpinnings of these rare diseases and to identify how existing drugs can target these specific mechanisms. By repurposing drugs, the Rare Base initiative seeks to provide quicker, more accessible treatment solutions for patients who often have limited options due to the rarity of their conditions.
Jax Labs
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JAX Rare Disease Translational Center has accepted the YWHAG variant project. The primary goal is to establish human disease models in the mouse where none exist and to advance therapeutics by matching as closely as possible disease characteristics in the mice with those of afflicted patients. The mouse strain will contain the human variant of interest c.394C>T, p.Arg132Cys as well as short stretch of flanking human DNA sequence to facilitate any future therapeutic strategy that might be considered that requires human sequences in the mouse.
The early phases of the project will include a targeting design phase, a CRISPR engineering phase, and a colony expansion phase. These steps can each take up to 3-6 months to complete.
Florida State University
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The project aims to develop and validate new animal and human cellular models to study how YWHAG mutations contribute to Developmental and Epileptic Encephalopathies (DEEs). By leveraging genetic and viral-mediated approaches, researchers will investigate the molecular and neurobiological mechanisms underlying the disease. Previous studies in mouse models suggest that a deficiency in 14-3-3 proteins leads to molecular, synaptic, and behavioral alterations. This project seeks to build upon those findings, using advanced models to better understand how YWHAG mutations cause childhood epilepsy and developmental impairments.
Visit - https://med.fsu.edu/iprd/developmental-and-epileptic-encephalopathies
Czech Centre for Phenogenomics
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The Czech Centre for Phenogenomics (CCP) is at the forefront of creating and analyzing mouse models to advance biomedical research. In collaboration with the International Mouse Phenotyping Consortium (IMPC), CCP employs standardized phenotyping protocols to systematically assess gene functions. Through a crucial grant award, CCP's RD-Factory program has prioritized the YWHAG gene. By developing precise mouse models with targeted YWHAG mutations, CCP aims to elucidate the gene's role in disease manifestation, thereby contributing to the identification of potential therapeutic strategies for affected individuals.
The phenotyping module at CCP offers a comprehensive suite of tools for the physiological and morphological assessment of experimental mice in a controlled environment. Their experienced staff conducts a wide variety of standardized tests and services. By integrating these advanced phenotyping techniques, CCP's research on YWHAG mouse models aims to uncover the physiological and behavioral manifestations resulting from YWHAG mutations. This comprehensive approach is expected to shed light on the gene's role in neurological functions and its potential link to epileptic encephalopathy, paving the way for precision targeted therapeutic interventions.