Coordination Funds

鸡作为一种模式生物有着悠久的历史，许多开创性的发现都是在这个物种中取得的。在免疫学的背景下，例如，B细胞首先被发现是鸡体内的抗体产生细胞，在鸡胚胎中发现了移植物抗宿主病。此外，家禽是全世界人类饮食中最重要的蛋白质来源之一。大量的病原体感染鸡，威胁动物福利和食品安全。为了保护动物免受这些疾病的侵害，鸡接种了许多疫苗，被认为是地球上接种疫苗最多的物种；然而，潜在的免疫反应在很大程度上仍然未知。这个研究单位的目的是为了更好地了解禽类免疫系统。为了实现这一目标，我们将重点关注适应性免疫反应及其与最相关病原体的相互作用。我们将利用最近产生的缺乏关键免疫细胞的转基因鸡，结合重要的感染模型来解剖鸡的免疫反应。这包括B细胞、αβ T细胞和γδ T细胞敲除鸡，以及沙门氏菌、传染性法氏囊病病毒（IBDV）、马瑞克病病毒（MDV）和不同的原生动物物种，包括艾美耳球虫。同时，我们将利用最近发现的鸡FOXP3作为标记物来表征调节性T细胞，并进一步研究自然杀伤细胞在鸟类中的作用。此外，我们将首次使用免疫肽组学方法，利用我们最近开发的B细胞和T细胞培养系统，在感染MDV和IBDV时，从鸡主要组织相容性复合体（MHC）呈现的病原体中鉴定肽。除此之外，我们将开发采用基因敲除鸡和新一代基于测序的MHC基因分型系统的过继转移方法，以解剖疫苗接种和随后的病原体挑战时的免疫反应。这将使我们能够识别和表征对重要病原体提供保护的细胞群。研究单位成员的独特专业知识、新型转基因鸡、感染模型和最先进的免疫工具是一个特殊的组合，将有助于拟议工作的成功，并将为鸟类免疫系统提供重要的见解。

The chicken has a long history as a model organism and many seminal discoveries were made in this species. In the context of immunology, for example B cells were first discovered as antibody producing cells in chickens and graft versus host disease was identified in chicken embryos. In addition, poultry is one of the most important protein sources in the human diet worldwide. A plethora of pathogens infect chickens and threaten animal welfare and food safety. To protect the animals from these diseases, chickens receive many vaccines and are considered the most vaccinated species on earth; however, the underlying immune responses remain largely unknown.The objective of this research unit is to provide a better understanding of the avian immune system. To achieve this, we will focus on the adaptive immune response and its interactions with the most relevant pathogens. We will dissect the chicken immune response using recently generated genetically modified chickens lacking critical immune cells in combination with important infection models. This includes B cell, αβ T cell and γδ T cell knockout chickens as well as Salmonella, Infectious bursal disease virus (IBDV), Marek Disease Virus (MDV), and different protozoa species including Eimeria spp.. Simultaneously, we will characterize regulatory T cells by using the recently discovered chicken FOXP3 as a marker and further investigate the role of natural killer cells in birds. In addition, we will use for the first time immunopeptidomics approaches to identify peptides from pathogen presented by the chicken major histocompatibility complex (MHC) using our recently developed B and T cell culture systems upon infection with MDV and IBDV. Beyond this, we will develop adoptive transfer approaches using knockout chickens and a novel next generation sequencing-based MHC genotyping system to dissect the immune responses upon vaccination and subsequent pathogen challenges. This will allow us to identify and characterize the cell populations that provide protection against important pathogens. Taken together, the unique expertise of the research unit members, novel genetically modified chickens, infection models and state-of-the-art immunological tools is an exceptional combination that will contribute the success of the proposed work and will provide important insights into the avian immune system.