LATTICE SIM2 SUPER-RESOLUTION IMAGING OF DYNAMIC CELLULAR PROCESSES DURING REGENERATION AND REPAIR
Lead Research Organisation:
University of Edinburgh
Department Name: MRC Centre for Regenerative Medicine
Abstract
Bioimaging is a key experimental technique that enables scientists to precisely observe the molecular mechanisms underpinning normal cell function, as well as cellular dysfunction in aging, injury or disease. As cells and tissues are highly dynamic, it is vital to track processes across time. However, too often our approaches to understand or engineer cells are hampered by only being able to assess and quantify single time-point. These snapshots, combined with the limited resolution of conventional microscopy, mean we cannot observe fundamental cellular processes within the cell - such as gene activation, signalling protein scaffolds and dynamic cell interactions (e.g., immune cells).
Super-resolution imaging can address these challenges. While this Nobel Prize winning methodology has transformed many areas of biology, until recently it has primarily been focussed on fixed cells or tissues, which needed to be processed and embedded using special methods. Thus, imaging of dynamic processes in live cells has been challenging. A technique known as Lattice SIM (structured illumination microscopy) can be used in live cells, as it is a gentler approach. It is also compatible with standard samples and labelling methods. Recent technology developed by Zeiss has now significantly enhanced the speed and resolution of previous SIM approaches. The technique has been termed Lattice SIM-2 and is implemented in the Elyra 7 microscope from Zeiss. This Superresolution microscope is capable of unprecedented live cell microscopy. With double the SIM resolution and ability to perform high speed imaging (>200 frames per second), we can generate time-lapse movies of specific cellular processes for the first time. This offers many opportunities to better understand and track natural or synthetic/engineered cellular processes.
This will be a step change for many of Edinburgh researchers. There are three research areas where the Elyra can be immediately deployed: 1) gene regulation; 2) intracellular signalling; 3) cell-cell communication. The faster, gentler, and higher resolution imaging means we can explore these processes in virtually any biological sample, including: developing embryos, primary stem cell cultures, immune cell co-culture models, and engineered/artificial materials.
The overarching objective of purchasing the Elyra 7 is to enhance our efforts to discover new biological mechanisms, and to engineer these for applications across the biosciences. Our vision is for the Elyra 7 platform to transform discovery science and stimulate new collaborations across model systems and distinct research questions. We will be one of the first institutions to secure the Elyra in Scotland. Due to the practicalities of live cell imaging, it is vital we have the Elyra in close geographical proximity to the largest range of researchers that can benefit from its capabilities. It will sit at the centre of our expertise in stem cell biology, mammalian synthetic biology, chemical biology, multiparametric high content image analysis, phenotypic drug discovery, and emerging artificial intelligent/machine learning approaches.
Super-resolution imaging can address these challenges. While this Nobel Prize winning methodology has transformed many areas of biology, until recently it has primarily been focussed on fixed cells or tissues, which needed to be processed and embedded using special methods. Thus, imaging of dynamic processes in live cells has been challenging. A technique known as Lattice SIM (structured illumination microscopy) can be used in live cells, as it is a gentler approach. It is also compatible with standard samples and labelling methods. Recent technology developed by Zeiss has now significantly enhanced the speed and resolution of previous SIM approaches. The technique has been termed Lattice SIM-2 and is implemented in the Elyra 7 microscope from Zeiss. This Superresolution microscope is capable of unprecedented live cell microscopy. With double the SIM resolution and ability to perform high speed imaging (>200 frames per second), we can generate time-lapse movies of specific cellular processes for the first time. This offers many opportunities to better understand and track natural or synthetic/engineered cellular processes.
This will be a step change for many of Edinburgh researchers. There are three research areas where the Elyra can be immediately deployed: 1) gene regulation; 2) intracellular signalling; 3) cell-cell communication. The faster, gentler, and higher resolution imaging means we can explore these processes in virtually any biological sample, including: developing embryos, primary stem cell cultures, immune cell co-culture models, and engineered/artificial materials.
The overarching objective of purchasing the Elyra 7 is to enhance our efforts to discover new biological mechanisms, and to engineer these for applications across the biosciences. Our vision is for the Elyra 7 platform to transform discovery science and stimulate new collaborations across model systems and distinct research questions. We will be one of the first institutions to secure the Elyra in Scotland. Due to the practicalities of live cell imaging, it is vital we have the Elyra in close geographical proximity to the largest range of researchers that can benefit from its capabilities. It will sit at the centre of our expertise in stem cell biology, mammalian synthetic biology, chemical biology, multiparametric high content image analysis, phenotypic drug discovery, and emerging artificial intelligent/machine learning approaches.
Technical Summary
Our understanding of many fundamental cellular processes has been enhanced through directly observation in live cells with microscopy at nanoscale resolution. The recent release of the Lattice SIM2 super-resolution microscope from Zeiss provides an innovative, user-friendly technology that allows gentle (non-destructive) SR imaging, enabling dynamic tracking of 60 nm organelles and cellular structures in living cells with unprecedented spatio-temporal resolution. This will open significant opportunities for many discovery research groups in Edinburgh, particularly those BBSRC-funded researchers exploring fundamental cellular mechanisms. The consortium of co-applicants was chosen to span complementary research questions, multidisciplinary expertise and research Centres. The focus is tackling fundamental understanding of key biological processes, using distinct experimental model systems and approaches (e.g., developmental biology, membrane trafficking, stem cell biology, genome editing, mammalian synthetic biology).
As the Elyra 7 can work with cells and precision cut tissue slices (up to 100 micrometers thick) and works with conventionally stained samples or fluorescent reporters, it immediately becomes tractable to many investigators and many distinct questions. Our co-investigators will focus on three core biological questions: 1) mechanisms of transcription (programming and reprogramming cell fate); 2) the dynamics of intracellular signalling (particularly dynamic membrane trafficking events); 3) cell-cell communication (neuronal and immune). The Elyra represents an important, timely upgrade to SR imaging at UoE (across Colleges) and would enhance more generally the UK research efforts in mammalian synthetic biology and fundamental discovery science research - strategic priorities for the MRC/UKRI.
As the Elyra 7 can work with cells and precision cut tissue slices (up to 100 micrometers thick) and works with conventionally stained samples or fluorescent reporters, it immediately becomes tractable to many investigators and many distinct questions. Our co-investigators will focus on three core biological questions: 1) mechanisms of transcription (programming and reprogramming cell fate); 2) the dynamics of intracellular signalling (particularly dynamic membrane trafficking events); 3) cell-cell communication (neuronal and immune). The Elyra represents an important, timely upgrade to SR imaging at UoE (across Colleges) and would enhance more generally the UK research efforts in mammalian synthetic biology and fundamental discovery science research - strategic priorities for the MRC/UKRI.
