SFB 1149: Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma

SFB 1149：急性创伤后的危险反应、干扰因素和再生潜力

• 批准号: 251293561
• 金额: --
• 依托单位: Universität Ulm
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/251293561?language=en
• 关键词: SFB; 1149; Danger; Response; Disturbance

Trauma can affect any individual at any time. The subsequent danger response, modulated by various individual disturbance factors, strives to induce regenerative processes, but can also represent a major driver of complications and fatal outcome. In the 2nd funding period, the consortium provided many novel mechanistic insights in the trauma response. In the 3rd funding period, the focus of the CRC1149 remains on the most frequent injury patterns (TBI, thorax trauma, fracture). The profile of confounding factors is expanded to reflect the entire lifespan. The investigations address mechanisms of compromised regeneration processes, and aim to provide a detailed pathomechanistic understanding of the molecular trauma response. In many projects, including a transfer project, an emphasis is set on the translation of meaningful research results. The trauma research profile of the Ulm University campus will facilitate realization of the integrative and translational approaches. These include a cross-discipline Trauma Research Centre Ulm (ZTF) with the CRC1149 as its central pillar, the long-standing commitment of the Medical Faculty to cutting-edge research in trauma, and the recent founding of a new research building on Multidimensional Trauma Sciences (MTW). As compelling scientific and clinical challenges, we pursue the central hypotheses of the CRC1149, to: A) elucidate the danger response after trauma on a molecular, cellular, organ, and organism level; B) determine the influence of major disturbance factors (co-morbidities) on the trauma response; C) define mechanisms and potential of regeneration post trauma and adapt them to trauma management. These hypotheses are reflected on by three highly interactive project groups (A, B, C), one transfer project (T01), and one central platform (Z02), combining excellent basic-science, translational, and clinical expertise: Research group A will investigate the mechanisms of the spatial-temporal, neuroinflammatory, immune, and cellular acute danger responses post trauma, and the subsequent consequences on cross-talking organs. Research group B will address the modulation and perturbation of the trauma responses by relevant confounding factors, including co-morbidities (aging, diabetes, atherosclerosis, osteoporosis, Parkinson’s disease), lifestyle habits (ethanol), acute stress, and experienced psychosocial trauma (early life stress). Research group C aims to improve the resolving and regenerative capacity in models of fracture, wounds, TBI and peripheral nerve trauma, accomplished by immune cells, stress hormones, progenitor cells and genetic regulators. In cooperation with a start-up pharma, the transfer project investigates inhibition of thromboinflammation in human extra-corporal membrane oxygenation/hemodialysis ex vivo models. Most projects include mechanistic evaluation of promising novel therapeutic approaches with the final aim of reducing the burden of trauma for the individual and society.

创伤可以在任何时候影响任何人。随后的危险反应，由各种个体干扰因素调制，努力诱导再生过程，但也可以代表并发症和致命后果的主要驱动因素。在第二个资助期，该联盟在创伤反应方面提供了许多新的机制见解。在第三个资助期，CRC 1149的重点仍然是最常见的损伤模式（TBI、胸部创伤、骨折）。扩展混杂因素的概况以反映整个寿命。调查解决受损的再生过程的机制，并旨在提供一个详细的病理机制的分子创伤反应的理解。在许多项目中，包括转让项目，重点是翻译有意义的研究成果。乌尔姆大学校园的创伤研究概况将促进整合和转化方法的实现。其中包括一个跨学科的创伤研究中心乌尔姆（ZTF）与CRC 1149作为其中心支柱，医学系的长期承诺，在创伤的前沿研究，并在多维创伤科学（MTW）的新研究大楼最近成立。 作为引人注目的科学和临床挑战，我们追求CRC 1149的中心假设，以：A）在分子，细胞，器官和生物体水平上阐明创伤后的危险反应; B）确定主要干扰因素（共病）对创伤反应的影响; C）定义创伤后再生的机制和潜力，并使其适应创伤管理。 三个高度互动的项目组（A，B，C），一个转移项目（T01）和一个中心平台（Z 02）反映了这些假设，结合了优秀的基础科学，翻译和临床专业知识：研究组A将调查创伤后时空，神经炎症，免疫和细胞急性危险反应的机制，以及随后对交叉器官的后果。研究组B将讨论相关混杂因素对创伤反应的调节和干扰，包括共病（衰老、糖尿病、动脉粥样硬化、骨质疏松症、帕金森病）、生活习惯（乙醇）、急性应激和经历过的心理社会创伤（早期生活应激）。C研究组旨在通过免疫细胞、应激激素、祖细胞和遗传调节剂来提高骨折、伤口、TBI和周围神经创伤模型的分辨和再生能力。该转让项目与一家初创制药公司合作，研究了在人体体外膜氧合/血液透析离体模型中抑制血栓炎症的作用。大多数项目包括对有前途的新治疗方法的机械评估，最终目的是减轻个人和社会的创伤负担。