AMEMM · Assembly, Mechanism, and Evolution of Macromolecular Machinery""
FP7 — People (Marie Curie Actions)
- Duration
- 2014-05-01 → 2018-04-30
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
Life has evolved many molecular machines to perform mechanical tasks. Studying these machines promises insights into how machinery can generate force, how they assemble themselves, and how they evolved from simpler components. Ultimately this knowledge may inform synthetic biology projects to redesign existing, or evolve novel, machinery. Yet these insights have been hindered by our inability to visualize these machines as they occur in situ. The emergent technique of electron cryo-tomography, however, offers the ability to image this molecular machinery in situ, and will likely form the basis of much research on these machines due to its ability to resolve individual proteins within frozen living cells in three dimensions. Here I describe interdisciplinary work to dissect macromolecular machinery and understand its function and evolution using as 'testing ground' one of the most striking examples of molecular machinery, the bacterial flagellar motor. The flagellar motor is attached to a long filament that it spins to form a helical propellor, pushing the bacterium in favourable directions. Yet although the motor's many components and cellular role are known, the molecular mechanism of rotation and self-assembly remain enigmatic, and while its ancestry is established, how additional proteins are recruited to form novel machinery is poorly understood. Pseudo-atomic models of motors in situ will be generated using electron cryo-tomography together with development of tagging techniques to locate proteins. These structures will next be related to their mechanical output using single-molecule biophysical methods to understand the mechanical contributions of components. Finally, fundamental principles of the evolution of macromolecular machinery will be explored, both by studying recent elaborations upon motors in some bacteria, and by studying convergent evolution by the unrelated – yet analogous – archeaellum.""
Original text from CORDIS.
Participants
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union