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. In sum, the project could lead to the availability of re-engineered systems that are effective for antibiotic treatment or drug delivery.
Quelles sont les particularités de ce projet?
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).
Aim 1 made progress in understanding 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.
*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
Revue de presse
Personnes participant au projet
Dernière mise à jour de cette présentation du projet 13.03.2020