Development of novel computational tools and algorithms for realistic 3D visualization and modeling of non-membranous cellular organelles

最近，人们投入了大量的精力来了解不受膜限制的、非常小（约100纳米）的、由几十种蛋白质类型（如着丝点和中心粒）密集堆积而成的细胞结构的组织。越来越多的人认识到这些结构不仅起着结构性的作用，而且起着至关重要的信号功能，例如，在控制纺锤体组装检查点和有丝分裂退出网络中，这激起了最近的兴趣。目前，对这些本质上是半致密蛋白质晶体的生物物理学理解是非常初级的。为了改进它，允许3D可视化和模拟的计算工具是绝对需要的。这个高度跨学科的项目定位在计算机科学、物理学和生物学的界面上，有一个雄心勃勃的目标，即适应和进一步开发工具，使现实的3D可视化和建模成为可能。具有数学和编程背景和经验的学生将使用开源平台CellPack (www.cellpack.org)，其具体目标是为着丝点和纺锤杆体（真菌中心粒）开发逼真的空间模型。开发的空间静态模型将用于与动态模拟的物理方法相结合，如分子动力学和布朗粒子动力学。这些方法最近发展迅速，我们在牛津大学物理系的合作者在将LAMMPS分子动力学平台应用于更简单和更传统的生物系统（如脂质膜和染色质）方面有很强的背景。该项目将为具有数学科学背景的学生提供一个独特的机会，以发展现代细胞生物学的新技能和知识。该项目预计将与爱丁堡惠康信托细胞生物学中心的研究以及我们在邓迪大学的合作者的研究产生强大的协同作用。

Recently much effort has been invested in understanding the organization of cellular structures that are not delimited by membrane, very small (~100 nm) in size and formed by dense packing of dozens of protein types, such as kinetochores and centrioles. This recent interest is fuelled by the growing recognition that these structures play not only structural but also crucial signaling functions, for example, in the control of the spindle assembly checkpoint and mitotic exit network. Presently, biophysical understanding of these essentially semi-dense protein crystals is very rudimentary. To improve it, computational tools allowing 3D visualization and simulation are absolutely required.This highly interdisciplinary project that is positioned on the interface of computer science, physics and biology has an ambitious goal to adapt and further develop tools that will allow both realistic 3D visualization and modeling. A student who is expected to possess background and experience in mathematics and programming will work with the open-source platform CellPack (www.cellpack.org) with the specific aim to develop realistic spatial models for the kinetochore and spindle pole body (fungal centrioles). The developed spatial static models will be used to interface with physical methods of dynamical simulation, such as molecular dynamics and Brownian particle dynamics. These methods have been burgeoning recently, and our collaborators at the U of E physics have a strong background in applying LAMMPS molecular dynamics platform to simpler and more conventional biological systems, such as lipid membranes and chromatin. This project will provide a unique opportunity for a student with the background in mathematical sciences to develop novel skills and knowledge of modern cell biology. The project is expected to have strong synergy with the research contacted in the Wellcome Trust Center for Cell Biology in Edinburgh as well as with the research of our collaborators at the University of Dundee.