Objectives: Technology development is indispensible in today’s healthcare system. The project focuses on two pillars of excellence in technology for enhancing human health:
first, the development of technology towards the next generation of affordable, simple & high-speed optical nanoscopy; and second,
the use of world-class imaging infrastructure (optical & electron) for pharmacologically and clinically relevant biological problems.
In this project, we propose a symbiotic marriage between technology drivers (Physics & Computer Science) and the core users of this technology (Medical Biology, Pharmacy, Clinical Medicine & Fishery Sciences) for doing pioneering cross-disciplinary research. The project benefits from & merges with the cutting-edge research infrastructures that are already present or are in the UiT roadmap, including both optical nanoscopes (SIM, dSTORM, STED)  and electron microscopes, (SEM & TEM). The long-term aim is to attract large external funding, such as ERC Grants & SFI, with commercialization/ spin-off as the possible outcomes.
SIM: Structured illumination microscopy; dSTORM: direct stochastic optical reconstruction microscopy; STED: Stimulated emission depletion microscopy; s-o-t-a: State-of-the-art
SEM: Scanning Electron microscopy, TEM: Transmission Electron microscopy
SFI: Center of Excellence, RCN (Research Council of Norway) Funding
Brief Synopsis of the project: We propose here to develop the next generation of optical nanoscopy for bio-medical and clinical applications. The technology roadmaps include chip-based optical nanoscopy (ERC Funded, Ahluwalia), label-free high-resolution microscopy (funded by SUI, Ahluwalia) and in-vivo nanoscopy. During the initial phase of the project (WP 1) we will focus our development activities on chip-based optical nanoscopy, whose future development will be made available to consortium members.
The cross-disciplinary aspect of the consortium will cover a full range of human health, from healthy birth (see WP 3) to healthy aging (WP 2). We also address health issues that affect the population at large through both disease, e.g., cholera (WP 1), and diet, by improving the healthiness of fish farmed for human consumption (WP 2). To ensure maximum impact, the consortiums have chosen high-impact bio-problems that could not be solved without the proposed cross-disciplinary collaborations and the infrastructure: -
a) Decoding exosome pathways in fishes and human using optical nanoscopy & electron microscopy (WP 2): Exosomes are secreted vesicles (30-150nm) containing RNA and protein cargos and they can serve as carriers shuttling diverse bioactive molecules between different cell types. The exosomes’ composition and functions are just beginning to be unravelled and exosomes are a hot research topic within the scientific community. This project intends to shed fundamental light on the mechanisms controlling exosome biogenesis/secretion from salmon head kidney-derived antigen-presenting cells (APCs) and scavenger endothelial cells (SECs) and their uptake and processing by same cell types using nanoscopy.
b) Sub-cellular anatomy of human embryonic pluripotent cells using optical nanoscopy (see WP 3): WP 3 targets clinical application of optical nanoscopy. Of the 400-500 embryos transferred after in vitro fertilization (IVF), only 30-35% succeed with pregnancy at the IVF Clinic, UNN. Embryos are transferred either at day 3 (8-cell stage) or day 5 (blastula stage). In our clinical experience the pregnancy rate increases up to 60% for embryos transferred at day 5. The molecules produced by cells in the blastula stage play a central role in activating endometrial receptivity for the embryo implantation, but the mechanisms are not fully understood. Successful pregnancy depends on the selection of “good embryos” that are primarily identified by morphological characteristics that lack a clear scientific basis. Here we will use nanoscopy to image the sub-cellular anatomy of human embryos and develop clinically relevant criteria for embryo selection before in utero transfer, which to our knowledge will be pioneering work in this field, with the potential to improve both the IVF success rate and fetal health.
c) Decoding signalling pathways in Vibrio cholera: Cholera is a pandemic disease that claims more than 100,000 deaths/year in the developing world; mainly children under 5. Here we will study fundamental questions in bacterial signal transduction in a Vibrio cholerae, both in laboratory & during infection.