Artificial Intelligence (AI)-enabled Cryogenic Electron Ptychography For Bio-macromolecule Imaging

低温透射电子显微镜（cryo-EM）与单粒子分析（SPA）是一种在近原子分辨率下三维（3D）可视化各种生物大分子的强大方法，可以直接了解其功能和机制。尽管取得了这些革命性的进步，但处理这些小的、异质的和/或灵活的分子或复合物仍然是一个挑战。一种新兴的策略是基于低温电子型图，最近我们已经证明了低剂量条件下生物样品的相重建。Ptychography是一种新兴的计算显微镜技术，用于获取分辨率超过透镜限制的图像，已应用于高分辨率x射线成像。由于其高相位灵敏度，对低电子剂量数据的鲁棒性和样品波函数的恢复，电子型图在快速发展的低温电镜领域代表了潜在的颠覆性变化。该项目的目的是提供一种新的计算图像恢复框架，以近原子分辨率在3D中可视化生物大分子。您将基于人工智能（AI）和机器学习技术，开发一个全新的计算方案，以显着加快耗时的从大量电子衍射重建，并恢复高分辨率的高保真生物大分子相对比图像。结合SPA，这种人工智能增强的型图可能会以公正和全面的方式揭示和检查小分子的3D结构。你将接触到应用数学、生物大分子、电子显微镜和低温学等不同的跨学科研究领域。你将体验到一个国际合作的环境，在那里你将与罗莎琳德富兰克林研究所的国际领先的电子显微镜专家密切合作。罗莎琳德富兰克林研究所是一个国家研究机构，致力于开发新技术来应对重要的卫生研究挑战。您将可以使用最先进的JEOL GrandARM，具有像差校正，冷冻级，这是英国第一个也是唯一用于此类工作的专用冷冻电镜。您还将与牛津大学结构生物学部门的世界领先的结构生物学家一起工作。

Cryogenic transmission electron microscopy (cryo-EM) with single-particle analysis (SPA) is a powerful method for visualizing a wide range of biological macromolecules in three dimensions (3D) at near-atomic resolution, which can provide direct insights into function and mechanism. Despite these revolutionary advances, it remains a challenge to deal with such small, heterogeneous and/or flexible molecules or complexes. An emerging strategy is based on cryogenic electron ptychography, which has been recently demonstrated by us for phase reconstruction of biological samples under low dose conditions. Ptychography is an emerging computational microscopy technique for acquiring images with resolution beyond the limits imposed by lenses, which has been applied to high resolution x-ray imaging. Due to its high phase-sensitivity, robustness to low electron dose data and the recovery of the sample wavefunction, electron ptychography represents a potentially disruptive change in the rapidly growing field of cryo-EM. The aim of this project is to provide a new computational image restoration framework for visualizing bio-macromolecules in 3D at near-atomic resolution. You will base upon artificial intelligence (AI) and machine learning techniques and develop a completely new computational scheme to dramatically speed up the time-consuming ptychographic reconstructions from a large quantity of electron diffraction, and recover high-fidelity phase-contrast images of biological macromolecules at high resolution. Combining with SPA, this AI-enhanced ptychography would potentially reveal and examine the 3D structures of the small molecules in an unbiased and comprehensive manner. You will be exposed to diverse and interdisciplinary research areas in applied mathematics, biological macromolecules, electron microscopy and cryogenics. You will experience an internationally collaborative environment, where you will closely collaborate with international-leading electron microscopists in the Rosalind Franklin Institute, a national research institute, dedicated to developing new technologies to tackle important health research challenges. You will have access to the state-of-the-art JEOL GrandARM with aberration correction, cryo stage, which is the very first and unique purpose-built cryo-EM in the UK for this category of work. You will also work with world-leading structural biologists in the Division of Structural Biology at the University of Oxford.