Dr Danielle Paul started her research career as a BHF funded PhD student using electron microscopy to study the structure of the filamentous proteins in cardiac muscle. She completed her PhD at Imperial College London in 2006 and then went on to the structural Biology department at the Institute of Cancer Research for her first post-doctoral position.
When her first son was born she and her family moved to Bristol and when her daughter was born in 2012 she took a career break for 2.5 years. Dr Paul returned to academia taking up a BHF Career Re-Entry fellowship in the school of Physiology, Pharmacology and Neuroscience at Bristol University in 2015. The focus of her lab’s work is to determine high resolution 3D models of the cardiac thin filament using state of the art image processing techniques and the recent advances made in the field of cryo-electron microscopy.
The recent “Cryo-EM revolution” has also produced a massive increase in the amount of data, in the form of EM images, with one session on the microscope producing up to 8TB. Powerful, well developed software exists for the analysis of data sets of this size when the object of study conforms to certain set of constraints i.e. they are either a globular protein or a helical filament. However, there are many harder to reach systems, such as the hybrid cases of globular proteins interacting with filaments. The number of biological and synthetic systems that involve such an arrangement is vast.
To this end, Dr Paul and her team will develop software to facilitate single particle analysis of Cryo-EM images of elongated / filamentous macromolecular complexes decorated with accessory globular proteins. The main objective is to create a self-contained image processing tool ‘PROOF: Software for the identification of accessory PROteins On Filaments’, that takes high resolution Cryo-EM movie data, automatically identifies filamentous proteins, straightens them if necessary and crucially locates the position of the accessory binding proteins. Segmentation/boxing of the filament can occur and ‘particles’ can then be extracted. These selected particles can then be fed into existing single particle image processing packages.