Investigation of the protective role of anti-PfGARP antibodies against severe malaria

该项目的目的是通过血清学和机器学习分析的结合，破译导致不同流行环境中抗pfgarp抗体产生严重疟疾保护作用的机制。该项目的目标是：1。使用截断的蛋白构建物建立并优化PfGARP血清学筛选平台，并使用我们的MagPix （Luminex）定量悬浮头阵列平台进行筛选2。利用筛查平台测量来自不同队列（高流行区和低流行区，印度和乌干达）的无症状、无并发症和严重疟疾感染个体血浆中抗pfgarp水平。通过进行机器学习分析，评估这些队列中抗pfgarp抗体的不同保护作用，包括临床（寄生虫血症、寄生虫生物量、血小板水平、MRI评估的脑肿胀、并发症、结局等）和生物学参数（选择毒性较小的寄生虫等）。开发抗pfgarp抗体检测试验，并评估其在印度临床环境中作为预后工具的潜力。Tetteh博士将负责血清学平台开发和优化以及样本筛选的相关研究。wassmer博士将使用广泛的临床和生物数据库来监督机器学习分析，以及在印度现场开发和评估抗pfgarp抗体检测测试。拟议的研究项目是高度跨学科的，两位导师将积极参与项目的各个方面。

The aim of the project is to decipher the mechanisms leading to severe malariaprotection conferred by anti-PfGARP antibodies in different endemic settings, using acombination of serological and machine learning analyses. The objectives of theproject are: 1. Set up and optimise a serological screening platform for PfGARP usingtruncated protein constructs and screened using our MagPix (Luminex) quantitativesuspension bead array platform 2. Leverage the screening platform to measure levelsof anti-PfGARP in the plasma of individuals with asymptomatic, uncomplicated andsevere malaria infection from different cohorts (high and low-endemic areas, India andUganda) 3. Assess the different protective effects of anti-PfGARP antibodies in thesecohorts by performing machine learning analyses including clinical (parasitaemia,parasite biomass, platelet levels, brain swelling assessed by MRI, complications,outcome, etc.) and biological parameters (selection of less virulent parasites, etc.) 4.Develop an anti-PfGARP antibody detection test and evaluate its potential as aprognostic tool in a clinical setting in India. Dr. Tetteh will oversee research related toserology platform development and optimization, as well as the sample screening. Dr.Wassmer will supervise the machine learning analysis using the extensive clinical andbiological database of the cohorts, as well as the development and assessment of anti-PfGARP antibody detection test on-site in India. The proposed research project is highlyinterdisciplinary and both supervisors will be actively engaged in all aspects of theproject.