Unravelling the physiological drivers of species accumulation and sensitivity for metals

金属是我们土壤中最常见的污染物之一。然而，这些潜在的毒物是否被生物体吸收，以及随后的毒性效应是什么，只有少数物种才知道-通常是那些容易在实验室中保存或在野外非常常见和广泛的物种。我们目前对不同物种中金属“积累”和相关“毒性”的理解范围有限，这使得我们难以预测和监测金属污染对生态系统的负面影响-无论是直接由于毒性，还是由于捕食者食用受污染的猎物。我们从过去的工作中了解到，即使在测试的有限物种中，金属积累和毒性也会有很大差异。此外，我们已经知道金属可能导致毒性的一些主要方式，以及细胞中的一些活性系统，通过这些系统可以通过“解毒”来防止这种影响。对于金属，这一过程通常与将金属的形式改变为惰性无机化合物，将其锁定在细胞内区室中或将其结合到不同的蛋白质和/或肽上有关。然而，我们目前不知道的是，这些机制和系统如何在物种之间形成对比，以及这种物种间的差异如何反过来导致积累程度和相关毒性效应的差异。在这个项目中，我们希望开发一个“框架”，统一理解金属如何被不同的土壤动物吸收，分布在组织之间，改变它们的化学联系，并对细胞，器官和整个生物体造成损害，最终导致对物种的毒性。我们的框架是基于在三个方面的发展理解：i）测量金属进入土壤动物组织并在土壤动物组织之间分布的速率。我们将通过分析主要组织中的金属水平来量化这一点，使用放射性标记的化合物来评估吸收和损失，并生成组织图来确定金属在体内的积累位置和数量。对于较大的无脊椎动物，我们将解剖组织，但对于较小的生物体，我们将使用最先进的激光辅助绘图技术。ii）评估金属进入生物体后改变其化学联系的方式，无论是通过化学反应，区室化还是通过结合。我们将通过分析不同组织样本中不同池中金属的化学形式，并通过使用X射线方法确定金属与其他元素和已知金属结合分子的共定位来测量这些过程。iii）评估暴露于不同形式的金属对细胞和组织造成的损害，这将通过评估与损害相关的生化反应并将这些反应与调节金属积累的途径和生物体内存在的化学形式联系起来来测量。我们将确定所造成的损害如何通过生物组织的各个层面转化为整个生物体水平的毒性。（锰、铅、铜和镉）在八种常见的具有生态重要性的土壤无脊椎动物物种中具有不同的主导化学性质和重要性，将使我们能够开发一种新的模型，描述导致金属积累和毒性的过程。这一方法将大大改善目前用于生态系统毒理学的方法，迄今为止，这些方法主要关注土壤中的外部金属化学及其对暴露的影响。此外，开发这种以生物为中心的模型将使我们能够将研究扩展到其他物种，从而更容易预测每个物种可能积累多少特定金属以及会产生什么样的毒性影响。这种能力将大大提高目前在比较生态毒理学中使用的方法。

Metals are one of the most common pollutants of our soils. However, whether these potential poisons are taken up by an organism and what the subsequent toxic effects are is only known for a small number of species - usually those easily maintained in the laboratory or very common and widespread in the field. The limited scope of our current understanding of metal "accumulation" and the linked "toxicity" in different species makes it difficult for us to predict and monitor the negative effects that metal pollution has on ecosystems - whether directly due to toxicity or as a result of predators eating contaminated prey. We know from past work that even among the limited species tested, metal accumulation and toxicity can vary greatly. Further, we already know some of the main ways that metals can cause toxicity and also some of the systems active in cells by which such effects can be prevented through "detoxification". For metals this process is often associated with changing the form of the metal to an inert inorganic compound, locking it away into intracellular compartments or binding it to different proteins and/or peptides. What we currently do not know, however, is how these mechanisms and systems contrast between species and how this inter-species variations, in turn, lead to differences in the extent of accumulation and linked toxic effect. In this project, we want to develop a "framework" that unifies understanding of how metals are taken up by different soil animals, distributed between tissues, change their chemical associations and cause damage to cells, organs and the organism as a whole, resulting ultimately in toxicity for a species. Our framework is based on developing understanding in three areas.i) Measuring the rates at which a metal enters into, and is distribute, between the tissue of soil animals. We will quantify this by analysing metal levels in major tissues, using radio-labelled compounds to assess uptake and loss and generating tissue maps to determine where and how much metal is accumulating in the body. For larger invertebrates we will dissect the tissue but for the smaller organisms we will use state-of-the-art laser assisted mapping technologies. ii) Assessing the way that metals change their chemical associations on up taken into an organism, either through chemical reactions, compartmentalisation or by binding. We will measure these processes by analysing the chemical form of the metals within different pools in separated tissue samples and by using X-ray methods that determine the co-localisation of metals with other elements and known metal binding molecules. iii) Evaluating the resultant damage to cells and tissues from exposure to the different metal forms.This will be measured by assessing biochemical responses associated with damage and linking these to the pathways that regulate metal accumulation and the chemical form present within the organism. We will determine how the damage caused translates through various levels of biological organisation to result in toxicity at the level of the whole organism.Studying these three aspects for four metals (manganese, lead, copper and cadmium) that have different dominant chemistries and essentialities in eight common and ecologically important soil invertebrate species, will allow us to develop a new model that describes the processes that lead to metal accumulation and toxicity. This approach will greatly improve on the current approaches used in ecosystem focused toxicology, which have so far focused on external metal chemistry in the soil and how this impacts on exposure. Further, developing this organism-focused model, will allow us to extend our studies to other species beyond those studied here to more easily predict how much of a given metal each may accumulate and just what toxic impacts will result. This capacity will significantly advance on the current approaches used in comparative ecotoxicology.