IM JAHR 2016 BEWILLIGTES PROJEKT

Effector delivery by Contractile Injection Machines – Microbials 2016

Redaktion

Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.


Kooperation

This project is one of the five winners of the call 2016 «Microbials – Direct Use of Micro-Organisms».

Project partners: University of Zürich; San Diego State University


Projektdaten

Projekt-Nr.: GRS-058/16
Förderbeitrag: CHF 352'000
davon Löhne: CHF 272'000
Bewilligung: 02.11.2016
Dauer: 01.2017 - 12.2019
Handlungsfeld: Microbials, seit 2016


Microbial Treatment of Solid Tumors – Microbials 2016
Projekt nummerGRS-059/16 BudgetCHF 400'000 VerantwortlichSimon Ittig Laufzeit01.2017 - 12.2018

Effector delivery by Contractile Injection Machines – Microbials 2016
Projekt nummerGRS-058/16 BudgetCHF 352'000 VerantwortlichMartin Pilhofer Laufzeit01.2017 - 12.2019

A Specific Mechanosensitive Bacterial Tumor Therapy – Microbials 2016
Projekt nummerGRS-057/16 BudgetCHF 374'000 VerantwortlichAlexandre Persat Laufzeit05.2017 - 04.2020

Microorganism-based Biosensor – Microbials 2016
Projekt nummerGRS-056/16 BudgetCHF 450'000 VerantwortlichJan Wendelin Stark Laufzeit01.2017 - 12.2019

Therapeutic Fungi – Microbials 2016
Projekt nummerGRS-055/16 BudgetCHF 480'000 VerantwortlichBenjamin Marsland Laufzeit01.2017 - 01.2020


Projektleitung

Prof. Dr. Martin Pilhofer, ETH Zurich, Biology, Molecular Biology & Biophysics, Otto-Stern-Weg 5, 8093 Zürich (Schweiz), pilhofer@biol.notexisting@nodomain.comethz.notexisting@nodomain.comch


Abstract

The delivery of effectors to the cytoplasm of target cells is an important problem in medicine (drug delivery) and biotechnology. Here, we will explore the use of bacterial contractile injection systems (BCIS) as a novel delivery vehicle. Our recent efforts identified potential effectors and showed that some BCIS can accommodate large effector payloads. In an interdisciplinary approach, we will 1) investigate the mechanism of effector targeting/binding in the inner tube and 2) re-engineer the system to accommodate novel effectors of choice. The results will help to develop a bioinformatic tool, which can be used to design novel effectors for the translocation by BCIS in the future.

Was ist das Besondere an diesem Projekt?

Innovative approach:
Based on their contractile, membrane-perforating properties, BCIS have been proposed for an application as novel antibacterial agents. The lack of knowledge on how considerable amounts of effectors can be loaded into a BCIS, however, has prevented to engineer them for the use for effector delivery to eukaryotic cells. This project will pave the way to load BCIS with many copies of an effector of choice.

Impact on drug delivery strategies and biotechnological applications:
The groundwork of this project to understand effector binding to the BCIS will have major impact on the function of BCIS in general. The possibility to predict how a given effector has to be engineered in order for it to be delivered to the target presents a novel strategy for effector delivery. This is significant for drug delivery to organisms, as well as for biotechnological tools that can be used for research. The design of cell line-specific BCIS will be the next step in the future, enabled by the work proposed in this project. This vision has great potential, since it might allow targeted treatment of only diseased cells (e.g. cancer cells).

Stand/Resultate

Aim 1 will be dedicated to the understanding of the relation of both effector candidates and the identification of binding and targeting domains. Aim 2 will be focused on using the insights from Aim 1 to re-engineer contractile injection systems and test their function.

Publikationen

*Shikuma NJ, *Antoshechkin I, Medeiros JM, Pilhofer M, Newman DK, Stepwise Metamorphosis of the Tubeworm Hydroides elegans is Mediated by a Bacterial Inducer and MAPK Signaling, PNAS;
*Shikuma NJ,*Pilhofer M, Weiss GL, Hadfield MG, Jensen GJ, Newman DK, Marine tubeworm metamorphosis induced by arrays of bacterial phage tail-like structures, Science

Medienecho

Tube Worm Larvae Use Prickly Bacterial Flowers to Choose Home, Scientific American, May 2015
Settlement Signal, The Scientist, January 2014
The Tale of a Tubeworm and a Biofilm, American Society For Microbiology, April 2014

Links

Pilhofer Lab

Am Projekt beteiligte Personen

João Medeiros
Fabian Eisenstein

Letzte Aktualisierung dieser Projektdarstellung

17.05.2017