Predicting Skin Interactions and Permeation of Chemical Agents using Computational Modelling

皮肤是人体最外层的屏障。大多数与身体接触的化学物质最初会通过与皮肤的相互作用来进行。因此，必须详细了解化学制剂与皮肤的相互作用，以便了解和改进从皮肤中去除化学制剂的过程。此外，进入人体的化学物质经常是通过渗透皮肤屏障来实现的。了解和预测这种渗透对于努力防止这种渗透发生，以及评估以前没有特征的危险化学制剂都是至关重要的。这个PHD项目将开发和验证一种新颖而独特的角质层计算模型。角质层既是皮肤的最外层，也是皮肤渗透的主要屏障。这使得它成为研究皮肤相互作用和渗透的理想选择。学生将涉及扩展粗粒ELBA脂质模型，以包括角质层膜的脂质。ELBA模型的独特之处在于，它将真实的静电相互作用(电荷和偶极子)合并到粗粒度脂质模型中，并允许执行混合原子/粗粒度模拟。随着这个模型的应用，我们的目标是克服以前角质层研究的局限性。该项目的最终目标将是提供一个关于化学剂与皮肤屏障的相互作用和渗透的预测性计算模型。

The skin is the outermost barrier for most of the human body. The majority of chemicals that come into contact with the body will initially do so through an interaction with the skin. It is imperative, therefore, that a detailed understanding of the interaction of chemical agents with the skin is obtained to inform and improve processes such as the removal of chemical agents from the skin. Furthermore, chemical agents that enter the body frequently do so through permeating this skin barrier. Understanding and predicting this permeation is vital in both trying to prevent this permeation from happening, and in the assessment of previously uncharacterised hazardous chemical agents. This PhD project will develop and validate a novel and unique computational model of the stratum corneum membrane. The stratum corneum is both the outermost layer of the skin and the main barrier to skin permeation. This makes it ideal to study for both skin interactions and permeation. The studentship will involve extending the coarse-grained ELBA lipid model to include the lipids of the stratum corneum membrane. The ELBA model is unique in that it incorporates realistic electrostatic interactions (charges and dipoles) within a coarse-grained lipid model, and also allows hybrid atomistic/coarse-grained simulations to be performed. With the application of this model we aim to overcome the limitations associated with previous studies of the stratum corneum. The ultimate aim of the project will be to provide a predictive computational model regarding the interaction and permeation of chemical agents with the skin barrier.