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Final Report Summary - TAMPTING (The biogenesis of tail-anchored membrane proteins: knowledge and exploitation)

TAMPting is a network of European and Israeli academics and SMEs with a common interest in the biogenesis of tail-anchored membrane (TA) proteins and the possibility of exploiting their unique biological properties in the context of liposome mediated drug delivery.

Project objectives:

1: To create a system for the efficient production of engineered TA proteins optimised for spontaneous insertion into preformed artificial membranes.
2: To exploit TA protein chimeras as ubiquitous membrane tethers that incorporate ligand mediated targeting functionality into drug-loaded liposomes.
3: To increase our understanding of how TA proteins are delivered to the mammalian endoplasmic reticulum.
4: To establish how the fidelity of TA protein biogenesis is maintained in prokaryotes and at the mitochondrial outer membrane.
5: To delineate the connectivity between TA protein biogenesis and the regulated degradation of mislocalised membrane proteins, and determine the cellular and physiological consequences of defects in these processes.

Main Scientific results

- Design, manufacture and purification of artificially engineered TA proteins that incorporate targeting motifs and are optimised for spontaneous membrane insertion.
- Incorporation of recombinant TA proteins into drug loaded liposomes and their functional analysis using cell culture models.
- Increased knowledge about TA protein biogenesis in mammals and a new understanding of the redundancy that underlies the delivery of this group of proteins to the endoplasmic reticulum
- The identification and study of bona fide TA proteins in prokaryotes and mitochondria.
- New insights into the cytosolic quality control networks that elicit the selective recognition and degradation of aberrant, misfolded and mislocalised membrane proteins

Training (see http://www.tampting.manchester.ac.uk/events/#.Wb_ihYoo8xc).

During the course of the network we held five dedicated training events, each hosted by one of our academic partners. Each of these events was comprised of an open seminar programme, together with a practical workshop focussing on a specialized technique and project presentations given by the fellows. Over 100 external participants attended the open components of our seminar programmes. All of our network fellows benefited from secondments to our partner SMEs and academic laboratories during the course of their projects. Our final keynote event was a one-day special interest symposium entitled “Targeting to the endoplasmic reticulum – tail-anchored proteins and beyond”, which we organised at the EMBO 2016 meeting held in in Mannheim. This international event highlighted the activities of the network to 90 external participants.

Key outcomes.

1. Enhanced understanding of the fundamental biological principles that underlie tail-anchored protein biogenesis from bacteria to man.
2. A ubiquitous platform for the incorporation of diverse targeting ligands into therapeutic liposomes preloaded with drug cargoes
3. A cohort of highly trained fellows who have benefitted from working in both academic and/or SME based environments.

The TAMPting project was promoted via a dedicated website (http://www.tampting.manchester.ac.uk/) and twitter feed and achieved additional publicity through the websites of our individual network participants. The project logo (see inset) created by the network members has been used in written dissemination and work relating to the project.

Reported by

THE UNIVERSITY OF MANCHESTER
United Kingdom

Subjects

Life Sciences
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