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Final Report Summary - AMEMM (Assembly, Mechanism, and Evolution of Macromolecular Machinery)

This document outlines progress made under my four-year FP7 CIG 'AMEMM' (Grant Agreement Number 630988). The proposal as originally submitted described aims to understand the assembly, mechanism, and evolution of molecular machines in life on earth. Specifically, I was interested in studying the evolution of the bacterial flagellar motor – a rotary molecular motor just tens of nanometres across – as a case-study in understanding fundamental principles of how molecular machines have evolved in life on earth.

To accomplish this I proposed an approach combining 3D electron microscopy imaging to visualize the structure of the machinery, physical measurements to assess the mechanical output of the machinery, and molecular ancestry studies to contextualize these observations against a robust ‘family tree’ of molecular machines. Three broad aims were proposed: first, I described aims to develop methods to structural characterize molecular machinery, using the bacterial flagellar motor as the model system. Secondly, I described aims to relate the structures of these machines to their mechanical output. Thirdly, I outlined strategies to relate these results to phylogenetics of the component proteins towards understanding the mechanistic aspects of their evolution.

Scientific progress has been excellent, and I accomplished the majority of my aims for the project. I have published work on the structure of diverse flagellar motors and directly related these structures to their mechanical output, and published a follow-up study describing a possible evolutionary pathway to this diversity. I have recruited a postdoc to study the analogous archaellar motor with the intent of identifying evolutionary fundamentals to both archaellar and bacterial flagellar evolution, and have recruited postdocs to continue to study the diversity and evolution of flagellar motors.

As a result, my research career development has progressed extremely well. Since award of the CIG I have been awarded multiple additional pieces of grant funding in total providing over £1 500 000 of funds to my lab. I have published a number of papers which have received considerable press coverage from the mainstream media, and I have delivered, or am invited to deliver, over thirty talks on this work at major international conferences and institutions. I have recruited four postdocs and four PhD students. These successes have lead me to pass the probationary period at Imperial College and be awarded promotion to Senior Lecturer.

Related information

Documents and Publications

Reported by

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
United Kingdom

Subjects

Life Sciences
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