The PHOQUS research programme involved the development of novel photonic tools and the application of these tools in the investigation of nuclear structure and dynamics, the control of cell behaviours at the tissue level in development and disease and in multispectral analysis of complex tissue level behaviours in preclinical diagnostics and drug development.
The objectives were to develop state-of-the-art technologies that will enable development of new imaging tools capable of investigating biological processes over a range of length scales from molecular and cellular to tissue organ and organism level scales. The broader goal is to make significant advances in the understanding of a range of outstanding biological problems.
Specific aims of this programme were:
- To develop new photonics tools that will feed into the design and development of smaller and more cost effective instruments. This in turn will lead to the more widespread adoption of these methods in life science and medical laboratories, giving better contrast in imaging and provide new capabilities in the manipulation of cells and tissues.
- To use these new tools to investigate the cellular and molecular dynamics which drive the process of cell division, especially chromosome segregation and structure and function of protein dynamics in nuclear functions, making extensive use of high resolution imaging and particle manipulation methodologies.
- To use newly developed imaging techniques to investigate the role of cell behaviours during embryo development and disease.
- To train a new generation of scientists in all these essential emerging technologies.
Many of these aims have been achieved. For further information, please see the ‘Publications’ page under ‘Scientific Deliverables’.
The programme developed and established new methodologies that allow the investigation of molecular and cellular dynamics at the tissue and organ level, a prerequisite for evaluation of novel drug targets in semi in vivo screening techniques as well as translation in important areas of medicine such as preclinical cancer and cardiovascular diagnostics. It initiated the development of novel photonic tools and their integration into compact commercially available instrumentation.
The programme is divided into closely inter-related areas of research.
- Photonics Tools
- Molecular and Cell Level Analysis
- Tissue Level Analysis
- Multimodal Spectral Analysis
WP1: Photonic tools will generate essential photonic tools needed for multi-photon imaging and spectral imaging, high strength nano Newton optical tweezers that will extend the ability of photonic manipulation of molecules to that of the manipulation of cells and tissues and novel nano-materials that will aid in generating high contrast and stable imaging reagents. The tools developed in this work package will be delivered to WPs 2, 3 and 4 and their applications demonstrated through the projects of the PHOQUS ESRs.
WP2: Molecular/Cell level Analysis will translate and implement novel photonic methods developed in WP1 into the research of fundamental properties of cells. Specific areas to be addressed are the mechanism of cell division, the control of DNA compaction and nuclear dynamics.
WP3: Tissue level Analysis will use novel imaging technologies to investigate cell behaviours that control tissue formation and function during development and in disease. Major methods to be used are novel forms of light sheet microscopy, multiphoton microscopy including 2nd and 3rd harmonic generation and photo acoustic microscopy. These methods will be used to investigate cell division and cell migration dynamics during embryonic development of chick and mouse embryos and to characterise cell dynamics and mechanics in the gut during the development of colon cancer.
WP4: Multimodal spectral Analysis will use multifunctional and multimodal imaging in improved diagnostics of preclinical disease especially cardiovascular disease and monitor tissue responses during drug development. It will combine different imaging modalities in multimodal platforms including terahertz imaging that will allow imaging at the tissue level.
The PHOQUS research programme will train 13 early stage researchers who will work together as a cohort to avoid becoming isolated in between physics and biology, and so developing a true identity as interdisciplinary scientists. Details of the research projects are listed below.