Investigating the processes of life in the cold: high resolution imaging of cellular proteostasis in Antarctic fish species

Lead Research Organisation: University of Cambridge
Department Name: Chemical Engineering and Biotechnology

Abstract

Antarctic ecosystems have evolved in a singularly isolated environment for millions of years. Due to a combination of geological and climatic factors, the Antarctic is the most isolated ecosystem on earth. This shielded environment has been stable for over 10 million years, giving rise to a remarkable diversity in adaptation to this continent. Antarctica has the highest proportion of endemic species of all ecosystems with around 17,000 marine invertebrate species. [1] Antarctic climate is however now facing an unprecedented threat. The Intergovernmental Panel on Climate Change's Five reasons for Concern [2] report the poles as being the fastest warming climates. The combined effects of an ecosystem that has been stable for millions of years and its projected rapidly changing climate make Antarctic cold-adapted species especially vulnerable to ocean climate change. The vulnerability of these species lies in the stability of their cellular machinery, and in particular the making, folding and maintaining of proteins. Very little is currently known about the mechanisms of protein stability around 0 C, and fewer still about this stability in complex organisms such as Antarctic fish. In order to understand the fundamental mechanisms of life in the cold, and to apply this understanding to incoming changes in Antarctic ecosystems, the British Antarctic Survey has partnered with several groups of the University of Cambridge and others in the UK in an ambitious and highly interdisciplinary project. As part of this collaboration, this PhD project is specifically aiming at the development of microscopy and fluorescence tools to study the protein lifecycle of Antarctic species. This PhD project will be focused on the development of a microscopy platform (year 1) along with fluorescence reporter methods (year 2). Indeed, microscopy at cold temperatures comes with technical challenges. These include the appropriate dosage of laser light to maintain physiological conditions in the cells, and a tight control of the microscope stage temperature so as to observe the samples across a range of conditions. We also expect challenges linked with the physics of the microscopy materials themselves (contraction of different parts, change in refractive indices... ). Once the microscope itself is adapted to polar conditions, we will also have to develop fluorescence tools operational around 0 C. These tools will be used to study factors affecting protein folding and stability, such as viscosity and cell chemistry. Two methods to measure intracellular viscosities will be tried, namely Single Particle Tracking (looking at the movement of one element over time) and Molecular Rotors (which rotate more or less quickly depending on cell conditions). We will use the combination of the microscopy and fluorescence techniques in the cold to link cellular phenotypes with the change of temperature experienced by the cell (year 3). This project is highly interdisciplinary and exists at the intersection of Biology, Physics and Engineering, bringing together a wide variety of scientific techniques. In terms of the EPSRC's strategies and research areas, this project touches on the following: Analytical sciences through the development of a new and unique microscopy platform, Biophysics and soft matter physics through the study of fundamental protein folding dynamics, or Sensors and Instrumentation through the development of protein tracking and temperature and viscosity measurements in

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 30/09/2019 30/03/2028
2408885 Studentship EP/S023046/1 30/09/2020 29/09/2024 Anne-Pia Myriam Marty