Multimodal imaging to resolve molecular pathology in tissue
- Reference number
- UKR22-0081
- Project leader
- Skoryk, Valeriia
- Start and end dates
- 220601-241231
- Amount granted
- 1 000 000 SEK
- Administrative organization
- Lund University
- Research area
- Life Sciences
Summary
Recent developments of new powerful approaches allow gathering more information for a better understanding of pathology. Therefore, there is a need for new protocols to allow efficient data analysis and interpretation. The core of the project is to develop and validate a new multidimensional approach that will use high-resolution X-ray tomography to first gather a comprehensive three-dimensional overview of the tissue biopsy at the micrometer scale, which can be used to specifically select tissue areas to be subjected for multiscale analysis (e.g. altered versus normal architecture from patients with disease). We will use label-free analysis techniques (e.g. infrared and second harmonic imaging) to allow for non-destructive assessment of the same sample. Next, we will use label-dependent immunochemistry to molecularly determine the location of specific proteins and label-free techniques that can give non-biased and more comprehensive overviews of the molecular changes accompanying structural level changes. Thus, we expect to produce protocols for cross-corelative analysis of the data produced by the combination of label-free and downstream label-dependent analysis techniques applied to the same tissue sample which will allow for complete information about disease onset. Understanding the meaning of infrared spectroscopy data and how they relate to disease will provide a new tool for pathological and research assessment of clinical biopsies.
Popular science description
An increasing number of fundamental research focused on related in vitro models, perhaps with methodological, technical, or computational bents working on crucial and fundamental questions of the disease mechanisms. However, such basic research is being partially abstracted from the clinical context. This project is aimed to develop a new multidisciplinary approach to profile early changes in tissue and link them with pathological changes. We propose a novel multimodal and multiscale project that combines high spatial resolution X-ray tomography of the organ, identification of pathological features such as molecules and their conformational states with downstream imaging followed by integrative analysis. The recent development of new powerful approaches allows gathering more information for a better understanding of pathology. Therefore, there is a need for new protocols to allow efficient data analysis and interpretation. The core of the project is to develop new protocols through newly established collaboration between host groups, and, with the help of advanced method combination, to gain new knowledge about the role of organ architecture in disease development. Another great motivation for the new method development lies in a strong need for efficient use of costly resources for medical applications. Thus, if successful, we will gain more knowledge about two terminal diseases and help other researchers use costly resources more effectively. The interdisciplinary elements of the proposal include tomography, spectroscopy, and, importantly, medical expertise in human pathology. Using these techniques in a correlative way, we aim at understanding the relationship between structural and molecular changes relevant and specific to disease is a key to treating pathology.