Liquid handling automated workstation for cell based assays

我们是一个由五个研究小组组成的团队，研究范围广泛，涉及生物学和医学之间的界面，特别是细菌病原体的细胞和分子生物学，抗菌剂和抗真菌剂，宿主-病原体相互作用和癌症生物学。虽然我们研究的主题非常多样化，但我们有一个共同的目标，即应用创新的高通量方法来解决我们的研究问题。为此，我们申请资金支持，建立一个尖端的液体处理自动化工作站。利用这种专门设计用于开发新型高通量细胞检测的仪器，我们建议：•对药物组合对革兰氏阴性细菌病原体的杀菌效果进行大规模评估，从而为对抗抗生素耐药性的惊人增长提供新的见解。对于少数有效的协同组合，我们建议重新评估它们对持久性革兰氏阴性病原体的细胞内功效，这些病原体越来越被认为会导致复发性感染。细菌细胞死亡的潜在机制将利用细菌突变文库和传统分子生物学技术进行研究。•探索大型化合物文库，系统地研究i)胃肠道细菌病原体的特定应激反应机制-外排泵，小RNA调节因子，小蛋白质-以及它们如何与耐药性和与人类宿主的相互作用相关；Ii)宿主代谢如何对引起性传播疾病的细胞内病原体感染作出反应；Iii)癌症特异性蛋白-蛋白相互作用的潜在抑制剂。•建立一个大型且特征明确的念珠菌分离株收集，从而阐明目前德国最普遍的危及生命的真菌病原体之一的抗真菌耐药性和流行病学情况。自动化工作站-我们目前还没有进入-是工具来完成所描述的项目，因此它将极大地支持我们的研究。

We are a team of five research groups working on a wide range of topics at the interface between Biology and Medicine, specifically on cell and molecular biology of bacterial pathogens, antimicrobials and antifungals, host-pathogen interactions and cancer biology. While working on largely diverse topics, we share a common goal of applying innovative high-throughput approaches to tackle our research questions. In order to do so, we hereby apply for financial support for establishing a cutting-edge liquid handling automated workstation. With this instrumentation specially designed to develop novel high-throughput cell based assays, we propose to:• Perform a large-scale assessment the bactericidal effect of drug combinations against gram-negative bacterial pathogens, therefore providing new insights for fighting the alarming rise of antibiotic resistance. For a handful of potent synergistic combinations, we propose to re-assess their intracellular efficacy against persistent gram-negative pathogens, which are increasingly acknowledged to cause relapsing infections. The underlying mechanisms of bacterial cell death will be investigated using bacterial mutant libraries and conventional molecular biology techniques.• Explore large compound libraries to systematically investigate i) particular stress-response mechanisms in gastrointestinal bacterial pathogens – efflux pumps, small RNA regulators, small proteins – and how they relate to drug resistance and interaction with the human host; ii) how the host metabolism rewires in response to infection by intracellular pathogens which cause sexually transmitted diseases; iii) potential inhibitors of cancer specific protein-protein interactions.• Establish a large and well-characterised Candida spp. isolate collection, therefore elucidating the current antifungal resistance and epidemiological situation of one of the most prevalent life-threatening fungal pathogens in Germany.The automated workstation – to which we currently have no access – is instrumental to accomplish the described projects, and it would therefore tremendously support our research.