BlueCryo Image Processing Computing Cluster

BlueCryo 图像处理计算集群

基本信息

批准号：
BB/R000484/1
负责人：
Christiane Berger-Schaffitzel
金额：
$ 38.23万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR000484%2F1
关键词：
BlueCryo Image Processing Computing Cluster

项目摘要

Imaging biomolecules at the molecular level to visualize their atomic details is essential to understand how they function in health and disease. Among the techniques capable of imaging biomolecules, electron cryo-microscopy (cryo-EM) has emerged as exceptionally powerful. New direct electron detectors, better microscopes and powerful processing software for the images recorded with this new hardware has led to a genuine revolution in cryo-EM. With these advances it is now possible to determine macromolecular structures at near-atomic resolution by cryo-EM, revealing essential molecular detail. High-resolution structural insight into molecular complexes, and also entire cells and even tissues, provide vital understanding of the molecular mechanisms of life. Until recently, high-resolution cryo-EM was not possible in the South-West due to the lack of a suitable cryo-microscope. In 2017, we answer this unmet need by opening a South West Regional Facility for High-Resolution Cryo-EM at University of Bristol, equipped with state-of-the-art hardware. This will enable us to collect several terabytes of images or movies per day of successful data collection. To fully exploit the potential of this facility, and to maintain and increase our competitive posture, we must complement the state-of-the-art cryo-microscope with equally powerful high-performance computing (HPC) for image processing. Processing of the terabytes of images is so computation-intense that existing HPC infrastructure can by no means match the computation requirements of the new EM user community.Therefore, to resolve this bottleneck, we ask here for funding of a computing cluster dedicated to image processing of cryo-EM data sets (BlueCryo). BlueCryo will enable researchers at University of Bristol to determine important structures by single particle cryo-EM and tomography, to interpret these structures using cutting-edge molecular modelling and to analyse the functional dynamics of the biological systems by state-of-the-art simulation methods. The BlueCryo HPC cluster will support the work of many researchers to accelerate their ambitious research, many of them funded by the BBSRC. The new resource will be instrumental for the discovery of new mechanisms of gene expression, to study protein transport into and across membranes, to understand the mechanism of secretion systems which play a crucial role in bacterial infections, and to illuminate a wide range of other important molecular processes responsible for biological function (and malfunction) in our cells. Moreover, the HPC cluster will critically support rational design of entirely novel proteins and peptide assemblies with tailor-made function, in vaccinology, drug delivery and drug discovery. Importantly, the new BlueCryo computing resource, together with the cryo-microscope, will further entice researchers from diverse life-science areas to partake in the cryo-EM revolution and generate new and exciting research synergies all across the South-West and beyond.Our work has broad implications for multiple areas within the BBSRC remit including synthetic biology, basic bioscience underpinning normal human and animal health and infection. The projects cover areas of direct relevance to BBSRC remit and strategy. The proposal includes researchers with a strong track record of BBSRC funding. Early career researchers and a re-entry fellow are part of our team. Clearly, the computing cluster will not only decisively advance the research here proposed, and generate new programmes, synergies and collaborations. It will also enable us to engage in many other important scientific questions and to train new users and students. Thus, we expect to derive significant additional use in many areas of basic and applied research at University of Bristol, the South-West and beyond.

在分子水平上成像生物分子以可视化其原子细节对于了解它们在健康和疾病中的作用至关重要。在能够成像生物分子的技术中，电子冷冻 - 微镜（Cryo-EM）已经出现为异常强大。新的直接电子探测器，更好的显微镜和功能强大的处理软件，用于使用此新硬件录制的图像，导致了Cryo-EM的真正革命。通过这些进步，现在可以通过低原子分辨率确定大分子结构，从而揭示基本的分子细节。对分子复合物，整个细胞甚至组织的高分辨率结构洞察力，提供了对生命分子机制的重要理解。直到最近，由于缺乏合适的冷冻微镜，在西南部还无法使用高分辨率的冷冻EM。在2017年，我们通过在布里斯托尔大学（University of Bristol）的高分辨率低分辨率EM开设西南地区设施，并配备了最先进的硬件，以解决这一未满足的需求。这将使我们能够每天收集成功的数据收集，以收集几种图像或电影。为了充分利用该设施的潜力，并维持和提高竞争性姿势，我们必须使用同样强大的高性能计算（HPC）来补充最先进的冷冻微镜，以进行图像处理。对图像的Terabytes的处理是如此强大，以至于现有的HPC基础架构绝对不能符合新的EM用户社区的计算要求。因此，要解决此瓶颈，我们在这里要求用于计算群集的资金，用于专门用于Cryo-Em数据集的图像处理（BlueCyo）。 Bluecryo将使布里斯托尔大学的研究人员通过单个粒子冷冻EM和层析成像来确定重要的结构，以使用最先进的分子建模来解释这些结构，并通过最新的模拟方法分析生物系统的功能动力学。 Bluecryo HPC群集将支持许多研究人员加速其雄心勃勃的研究的工作，其中许多研究由BBSRC资助。新资源将有助于发现基因表达的新机制，研究蛋白质侵入和跨膜的蛋白质传输，以了解分泌系统的机制，这些机制在细菌感染中起着至关重要的作用，并照亮了我们细胞中负责生物学功能（和故障）的其他广泛的重要分子过程。此外，HPC簇将在疫苗学，药物递送和药物发现方面具有裁缝功能的全新蛋白质和肽组件的合理设计。重要的是，新的BlueCryo计算资源以及冷冻微观的计算资源将进一步吸引从不同的生活科学领域的研究人员参与冷冻EM革命，并在整个西南部及其他地区产生新的和令人兴奋的研究Synergies。您的工作对BBSRC恢复良好的良好领域具有广泛的影响，包括BBSRC恢复良好的生物学，包括合成生物学，基础生物学及其不足的范围，并不足以适应于良好的健康状况。这些项目涵盖了与BBSRC汇款和战略直接相关的领域。该提案包括具有BBSRC资金良好记录的研究人员。早期的职业研究人员和重新进入研究员是我们团队的一部分。显然，计算集群不仅将果断地推进这里提出的研究，并生成新的程序，协同作用和协作。这也将使我们能够参与许多其他重要的科学问题，并培训新的用户和学生。因此，我们期望在布里斯托尔大学，西南及其他地区的许多基础研究和应用研究中获得大量额外使用。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage.

DOI：
10.1038/s41467-021-26610-3
发表时间：
2021-11-02
期刊：
Nature communications
影响因子：
16.6
作者：
Conners R;McLaren M;Łapińska U;Sanders K;Stone MRL;Blaskovich MAT;Pagliara S;Daum B;Rakonjac J;Gold VAM
通讯作者：
Gold VAM

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

DOI：
10.1093/abt/tbad024
发表时间：
2023-11-10
期刊：
ANTIBODY THERAPEUTICS
影响因子：
0
作者：
Buzas, Dora;Bunzel, Adrian H.;Berger, Imre
通讯作者：
Berger, Imre

Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis

DOI：
10.1101/589077
发表时间：
2020-01-01
期刊：
bioRxiv
影响因子：
0
作者：
Alvira, S.;Watkins, DW.;Collinson, I.
通讯作者：
Collinson, I.

Cryo-electron microscopy of the f1 filamentous phage reveals insights into viral infection and assembly.

DOI：
10.1038/s41467-023-37915-w
发表时间：
2023-05-11
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Conners, Rebecca;Leon-Quezada, Rayen Ignacia;McLaren, Mathew;Bennett, Nicholas J.;Daum, Bertram;Rakonjac, Jasna;Gold, Vicki A. M.
通讯作者：
Gold, Vicki A. M.

Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio.