Moving metals: Systematic characterization of metal transporters in Toxoplasma gondii

移动金属：弓形虫金属转运蛋白的系统表征

• 批准号: BB/W014947/1
• 负责人: Clare Harding
• 金额: $ 54.06万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW014947%2F1
• 关键词: Moving; metals; Systematic; characterization; metal

Cells require metals to create energy and to grow and divide. However, metals cannot pass through the membranes that surround our cells, and instead are transported across membranes by specialised proteins called transporters. This is true of the cells in our bodies, as well as the pathogens which infect us. I am interested in a single-celled parasite called Toxoplasma gondii. This parasite can live in any of the different cells or tissues in our body, making it exceptionally good at adapting to its environment. We know that Toxoplasma requires metals, but we don't know how they are transporting these metals from our cells into the parasite. In this project, we will identify parasite transporter proteins, and investigate how they are functioning within Toxoplasma. To do this, we will first investigate some metal transporters that we know about because they are similar to ones studied in other organisms. We will find out what happens when we remove these transporters, and where they are localised on the cell. But we predict there are types of transporter proteins that are not similar to those we know about. To find these is more challenging. We will make a collection of parasites with every transporter (about 200) deleted. We will grow this collection of parasites in different conditions (e.g. with different levels of metals). By measuring how much they grow, we can find transporters that, when we delete them, change the parasite's ability to grow under different metal conditions. This will help us identify which transporters are important to the parasite in different environments.To investigate how these transporter proteins function, we will also take other approaches. We will see if our parasite transporters can replace ones that are well-studied in yeast. If they can it means that they are likely to have the same or a similar function. We will also put our transporters into frog eggs. Frog eggs are special because they do not have any transporters of their own, so using these large cells we can measure very precisely how our parasite transporters are working to move metals into and out of the cell.In this project, we will learn the identity of Toxoplasma metal transporters and how they function in these parasites. Because metals are essential to the parasite, if we understand this we will understand more about how the parasite produces energy and how it interacts with the cells or our body. This knowledge will help us in the future discover new way to treat Toxoplasma, and possibly its related parasite Plasmodium, which causes malaria.

细胞需要金属来产生能量以及生长和分裂。然而，金属不能穿过我们细胞周围的膜，而是通过称为转运蛋白的专门蛋白质跨膜转运。我们体内的细胞以及感染我们的病原体都是如此。我对一种名为弓形虫的单细胞寄生虫很感兴趣。这种寄生虫可以生活在我们体内任何不同的细胞或组织中，使其非常善于适应环境。我们知道弓形虫需要金属，但我们不知道它们如何将这些金属从我们的细胞转运到寄生虫体内。在这个项目中，我们将鉴定寄生虫转运蛋白，并研究它们在弓形虫中的功能。为了做到这一点，我们将首先研究我们所知道的一些金属转运蛋白，因为它们与其他生物体中研究的金属转运蛋白相似。我们将发现当我们移除这些转运蛋白时会发生什么，以及它们在细胞上的位置。但我们预测有一些类型的转运蛋白与我们所知道的不相似。找到这些是更具挑战性的。我们将收集每一个运输机（约200）删除的寄生虫。我们将在不同的条件下培养这些寄生虫（例如，不同水平的金属）。通过测量它们的生长量，我们可以找到转运蛋白，当我们删除它们时，改变寄生虫在不同金属条件下生长的能力。这将帮助我们确定哪些转运蛋白在不同的环境中对寄生虫是重要的。为了研究这些转运蛋白的功能，我们还将采取其他方法。我们将看看我们的寄生虫转运蛋白是否可以取代在酵母中得到充分研究的转运蛋白。如果它们可以，则意味着它们可能具有相同或相似的功能。我们还将把我们的运输工具放入青蛙卵中。青蛙卵是特殊的，因为它们没有自己的任何转运蛋白，所以使用这些大细胞，我们可以非常精确地测量我们的寄生虫转运蛋白是如何将金属移入和移出细胞的。在这个项目中，我们将了解弓形虫金属转运蛋白的身份以及它们在这些寄生虫中的功能。因为金属对寄生虫来说是必不可少的，如果我们了解这一点，我们将更多地了解寄生虫如何产生能量以及它如何与细胞或我们的身体相互作用。这些知识将帮助我们在未来发现治疗弓形虫的新方法，可能还有与之相关的导致疟疾的寄生虫疟原虫。