Supervisors: Dr Peng Wang

Summary:

Ptychography is an emerging computational microscopy technique used to acquire images with resolution beyond the limits imposed by the lenses in conventional low temperature (cryo-) electron microscopy (EM). It is known for its super-resolution and high contrast even in noisy conditions and has come about because of developments in sophisticated modelling and computational analysis. In particular, Single Particle Analysis (SPA) software is used to reconstruct exquisitely detailed 3D images of biological objects (the particles). In this project we will enhance the analysis still further by integrating GPU-enhanced ptychography into the SPA framework. This will enable us to overcome some current limitations in resolving small biological objects, such as proteins and enable researchers to work with diverse imaging modes. The advance will significantly enhance data quality, and push the boundaries of resolution. In summary this project will focus on developing new software with GPU acceleration to provide a more precise way of achieving 3D reconstructions of biological objects.

Background:

Single Particle Analysis (SPA) software is a critical tool in the field of biological imaging, especially for cryo-EM. It plays a pivotal role in extracting structural information from biological objects such as proteins, enabling the generation of high-resolution 3D reconstructions. However, traditional SPA techniques have primarily relied on conventional electron microscopy imaging at high defocus. The low contrast and signal-to-noise ratio in defocused EM images make it particularly challenging to achieve atomic-level resolution for small molecules. 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. Owing to its super-resolution and high contrast, robustness to noisy raw data and the recovery of the object wavefunction, it represents a potentially disruptive change in the rapidly growing field of cryo-EM biological imaging.

Project:

The primary objective of this project is to create advanced SPA imaging software with GPU acceleration, for the reconstruction of high resolution 3D images of biological objects, such as proteins. Our goal is to integrate the ptychographic protocol into the SPA workflow within the “RELION” framework, widely used open-source software for SPA 3D reconstruction. This integration, further empowered by the parallel processing power of GPUs, will allow researchers to work with various imaging modalities, significantly improving the quality of their data, and pushing the boundaries of resolution. The result could potentially be more accurate reconstructions of biological structures, such as proteins.

You will receive training in HetSys’ postgraduate programme to become a highly skilled computational scientist, comfortable in working in a stimulating interdisciplinary environment. Throughout this project, you will gain exposure to diverse research areas in applied mathematics, GPU software engineering and 3D electron microscopy. You will also experience an internationally collaborative environment, working closely with internationally-leading electron microscopists and companies dedicated to developing new technologies for addressing important health research challenges as well as with world-leading biologists, locally and nationally. Access to the state-of-the-art research technology platforms (RTP) including transmission EM and high performance computing (HPC) will be provided.

To discuss this project further contact: peng.wang.3@warwick.ac.uk