Antibody target identification and novel diagnostics

该项目将专注于识别特异性识别神经退行性疾病(ND)相关蛋白的自身抗体，如tau、淀粉样β蛋白(Aβ)、TDP-43、α-突触核蛋白和Huntingtin(HTT)及其蛋白毒性聚合体种类。将使用蛋白质微阵列和基于CRISPR/CAS9的流式细胞术方法对人类自身抗体进行筛选，以确定其特定的目标表位。在用生化和细胞生物学方法验证自身抗体与其靶标之间的相互作用后，我们将应用成熟的单分子检测技术，开发高灵敏度的诊断方法来检测生物液中的自身抗体。最后，我们的目标是利用我们的合作伙伴提供的样本进行概念验证研究，以检测NDS患者血清和/或脑脊液中潜在的与疾病相关的人类自身抗体。在这里建立的自身抗体靶标发现平台将能够识别与神经退行性疾病高度相关的新的自身抗体表位，并促进开发强大的诊断工具用于研究，并最终对临床样本进行常规检测。

This project will focus on the identification of autoantibodies that specifically recognize neurodegenerative disease (ND)-associated proteins such as tau, amyloid-beta (Aβ), TDP-43, α-synuclein and huntingtin (HTT) and their proteotoxic aggregate species. Human autoantibodies, some already identified or cloned in the Prüß laboratory and further ones to be newly discovered in this research unit, will be screened with protein microarrays and CRISPR/Cas9-based flow cytometry approaches to identify their specific target epitopes. After validating the interactions between autoantibodies and their targets with biochemical and cell biological methods, we will develop highly sensitive diagnostic assays for detecting autoantibodies in biofluids, applying established single molecule detection technologies. Finally, we aim to perform proof-of-concept studies with samples provided by our collaboration partners to detect potentially disease-relevant human autoantibodies in serum and/or CSF of patients with NDs. The autoantibody-target discovery platform established here will enable the identification of novel autoantibody epitopes with high relevance to neurodegenerative diseases and foster the development of powerful diagnostic tools for investigation, and eventually, routine testing of clinical samples.