Structural and Functional Analyses of the Full-length Insulin Receptor (IR) and Type 1 Insulin-like Growth Factor Receptor (IGF1R) in the Liganded Active State

配体活性状态下全长胰岛素受体 (IR) 和 1 型胰岛素样生长因子受体 (IGF1R) 的结构和功能分析

• 批准号: 10386663
• 负责人: Xiaochen Bai
• 金额: $ 5.16万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10386663
• 关键词: 3-Dimensional; Classification; Complex; Cryoelectron Microscopy; Data; Data Collection; Data Set; Data Storage and Retrieval; Devices; Electron Microscopy; Funding; Grant; Growth Factor Receptors; Housing; Image; Insulin Receptor; Insulin-Like Growth Factor Receptor; Lead; Length; Ligands; Methods; Molecular Conformation; Performance; Process; Structure; System; Time; computerized data processing; image processing; imaging modality; improved; parent project; particle; receptor

This application for supplemental grant is to request fund for purchasing a high performance GPU cluster for single particle cryo-EM data storage and processing, which is under the parent project that is focused on the understanding of the exact ligand induced activation mechanism of insulin receptor and IGF1R. In the last year, we have made tremendous progress toward finishing all the 3 aims of proposed project. Nevertheless, after I submitted the original proposal, our cryo-EM facility has been expanded significantly, currently housing 4 high-end electron microscopies, which is two times more than that one year ago. In addition, our cryo-EM facility has recently implemented a new data collection method with beam-image shift, which increases the throughput of data collection by another factor of 3. As a result, we can collect approximately 6 times more data in certain period, compared with one year ago. Thus, the current two old GPU servers in my lab would not allow us to process all newly generated cryo-EM data in a timely manner, which would lead to delay for the proposed project. Furthermore, with the improved data collection capability after our cryo-EM facility expands, we can generate 4-5 TB new cryo- EM data weekly. Such large amount of data cannot be stored in my old GPU servers for long term. By using an advanced GPU cluster that have 16 powerful GPU cards and 1000 TB storage space, I will be able to finish the processing of one full dataset in a few days. This will also allow me to try several recently developed 3D classification methods to distinguish the structures of full-length receptor/ligand complexes in different conformational states, which will be the key results in this proposed project. With the 1000 TB storage device, we could store more than 50 different datasets in the same time, meaning that each dataset can be stored in the GPU cluster for ~1 year before transferring to a permanent storage device. This would allow me to easily reprocess the data to improve our structures, as soon as a new method for image processing is developed.

本申请是为购买高性能GPU而申请的 单粒子冷冻电镜数据存储和处理集群，这是在母项目 其重点在于了解胰岛素的确切配体诱导的激活机制 受体和IGF 1 R。在过去的一年里，我们取得了巨大的进展， 三是提出项目目标。然而，在我提交了原始提案后，我们的冷冻EM 设施已大幅扩大，目前容纳4个高端电子显微镜， 是一年前的两倍。此外，我们的冷冻电镜设施最近 实现了一种新的数据采集方法与光束图像移位，这增加了 数据收集的吞吐量增加了3倍。因此，我们可以收集大约6 与一年前相比，某些时期的数据增加了一倍。因此，目前的两个老GPU 我实验室的服务器不允许我们及时处理所有新生成的冷冻EM数据， 这将导致拟议项目的延误。此外，随着改进的 数据收集能力在我们的低温EM设施扩大后，我们可以产生4-5 TB的新低温- 每周EM数据。如此大量的数据无法长期存储在我的旧GPU服务器中。 通过使用具有16个强大GPU卡和1000 TB存储空间的高级GPU集群， 将能够在几天内完成一个完整数据集的处理。这也能让我尝试 最近开发的几种3D分类方法，以区分全长的结构， 受体/配体复合物在不同的构象状态，这将是关键的结果， 拟议项目。使用1000 TB的存储设备，我们可以存储50多种不同的 数据集，这意味着每个数据集可以在GPU集群中存储约1 在转移到永久存储设备之前一年。这可以让我很容易地重新处理 一旦开发出一种新的图像处理方法，我们就可以利用这些数据来改进我们的结构。