(EPSRC DTP) How to see biological molecular nano-machines in motion − with development of 4-dimensional image reconstruction techniques

This project is to develop a mathematical solution to the problem to model the structure/s of a dynamic 3-dimensional (3D) object from 2D projection image data (therefore a 4-dimensional object, where the 4PthP dimension can be though of as time or progress of a reaction coordinate). This is particularly needed in the field of biological electron cryo-microscopy.

Biomolecules can operate as molecular nano-machines. They are flexible and change shape as part of their mechanism. To see their molecular structures we take fixed snap-shots of frozen samples using electron cryo-microscopy (cryoEM), which is the only imaging technique capable of direct imaging of these molecules and resolving their features at sub nanometre resolution.

Due to the damage caused by the imaging beam, only one image per molecule can be captured with high resolution information. The biological molecules are frozen in a thin layer of vitrified water, but may exist in multiple conformations or states. Different views will be given by the random orientations of molecules in solution.
Detailed molecular structures can be computed from cryoEM images of many thousands of individual molecules, provided they represent a unique structure or molecular conformation. If there are parts that adopt different positions, these will be blurred due to averaging over different conformations.

In this project the student will develop methods to overcome the current limitations by applying novel mathematics and computational approaches, giving a step change in our resolution of flexible biomolecules and so seeing nano-machines in action.

These techniques for 4-dimensional reconstruction will also be applicable to other tomography applications, such as X-ray computed tomography, medical imaging applications, and potentially many other imaging modalities. They will be particularly applicable in situations when there is sparse or missing data regions.


Entry Requirements:

Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/)