Most natural proteins lose their ability to function as temperature deviates from their optimal operating point. While the stability and function of proteins at ambient and high temperatures is well understood, the way in which proteins and proteostasis work in cold-adapted multicellular life is unknown. Consequently, it is unclear how cold-adapted organisms will respond to even slight changes in temperature.

My PhD project aims to help understand the stability of cold-adapted (psychrophilic) proteins and proteostasis in multicellular organisms to shifts in environmental conditions.
We start by (1) computationally modelling cold adaptation for single proteins with sequence modelling methods from natural language processing and consecutively (2) extend to the cellular level by modelling the interplay of these proteins in a metabolic model and leveraging ideas from graph machine learning.
We seek to answer the following research questions:
- What features in a protein's amino acid sequence and three dimensional structure underpin its functional stability at temperatures as low as -2 degrees C?
- How do the relevant individual proteins interact to enable cold-adapted multicellular life?
- How does the metabolic network of cold-adapted species respond to changes in temperature, which in turn have effects on cellular viscosity and protein stability?
We study these questions for the experimental system Harpagifer antarcticus, a small and abundant Antarctic fish, for which a fully sequenced and annotated genome became available in 2020.
Besides helping to decipher the fundamental question of how life works at low temperatures, an understanding of proteins and proteostasis in cold environments has wide-ranging environmental consequences. We highlight two: a biodiversity and a biotechnology aspect.

1) Understanding the risk to Antarctic biodiversity:
Cold ecosystems, such as the ocean depths, polar and alpine regions, cover around three-quarters of Earth's surface and consequently harbour much of Earth's biodiversity. The Antarctic ocean is a particularly precious treasure trove of biodiversity because it has effectively been separated from the rest of the world's ecosystem by the Southern Ocean circulation for over 20 Mio years. While the long evolutionary pressure has evolved Antarctic fish to survive the extreme cold, it has also left them poorly adapted to rapid environmental change. Indeed, many of these fish are unable to survive in water temperatures above 2-4 degrees C. Understanding the extent to which the proteome of Antarctic fishes (notothenioids) adapted to the cold will provide critical information on how even a slight warming of the Southern Ocean might disrupt key metabolic pathways in these temperature sensitive animals. Since notothenioids constitute over 90% of the fish biomass in Antarctic waters, they are a key link in many food chains and their fate strongly impacts the future of the Antarctic biosphere. The methods developed in this project could further lead to important insights on the climate-change related risks to other cold-adapted species.

2) Combatting climate change with biotechnology:
Furthermore, understanding cold-adapted proteins enables enzyme-engineering for emerging applications such as energy saving biotechnology processes. For instance, cold-adapted enzymes in laundry detergents already enabled low-temperature effective laundry detergents which curb the electricity consumption needed for heating water for laundry. In addition to their use in detergents, cold-adapted proteins holds the potential to develop sustainable low-energy biotechnology from the food industry over the bioremediation of wastewater to the synthesis of biofuel.