Systems that are not in equilibrium are ubiquitous but can be complex to describe. Systems at equilibrium are described with great success by statistical mechanics but there are no general theoretical framework for how closed many-body quantum systems evolve to reach such thermalised states. Examples range from the cooling of a cup of coffee to the emergence of structures in the early universe. Non-equilibrium (NEQ) processes are also important for quantum systems including quantum computers such as those based on superconducting qubits. Our experimental techniques allow many-body quantum systems to be prepared in precisely defined NEQ situations and then track their evolution towards equilibrium in unprecedented level of detail. The system that we will use to gain a better understanding of NEQ physics is a two-dimensional (2D) gas of atoms at temperatures of tens of nanokelvin. The properties of 2D systems are of central importance in physics and part of the Nobel prize for Physics (2016) was awarded to Kosterlitz and Thouless for their work on a phase transition in 2D systems that is named after them, the Berezinskii-Kosterlitz-Thouless (BKT) transition. This transition occurs as the 2D quantum gas is cooled and, at a certain temperature, it changes into a superfluid that flows without friction amongst other fascinating properties. The ultracold atoms are trapped in extremely well-controlled conditions thus enabling us to make definitive quantitative comparisons with theoretical expectations. Quantum systems confined to 2D are especially interesting for studying NEQ processes because the fluctuations, that are an inherent part of quantum mechanics, play a large role in preventing true long-range order. This approach will provide insights into similar phase transitions in other 2D systems such as thin-film superconductors and liquid crystals, and the quantum gas acts as a quantum simulator of 2D quantum physics in general. A key factor that enables the proposed investigation is the double-well potential for ultracold rubidium atoms that we have created by an innovative use of combined radiofrequency (RF) and static magnetic fields. With this technique we have realised a bilayer of 2D quantum gases where the inter-layer distance is controlled with a precision of tens of nanometres, which is impossible with alternative (optical) methods that are widely used. This allows the quantum coupling between two layers to be set to precise values, and we use the programmability of modern RF electronics to implement dynamical control of the double-well potential with nanosecond resolution. A further advantage of having two layers, is that we can use matter-wave interference of the ultracold atoms to probe the microscopic phase fluctuations of the system that are intrinsic in 2D quantum gases. This allows us to probe the local vortex density and first-order correlation functions which are the key to understanding BKT physics. Further technical improvement will allow the detection of higher-order correlations, as well as the full probability distribution function of the fluctuating observables, which represent the essence of quantum observables. Using this cold-atom apparatus as a 'quantum simulator' of many-body phases in 2D systems will provide fresh insights. These experimental techniques have been developed and refined to the level at which the quantum tunnelling between the two wells is controllable and this state-of-the-art apparatus enables the experimental investigation of long-standing research questions.

Newly born nerve cells, or neurons in the brain, contain a set of instructions written in their genes, which together with messages they receive from neighbouring neurons, guides their development. These factors will determine the type of neuron it will become and determine which other neurons it will make contacts with and form a neural circuit. Errors in the development of neural circuits at these early stages can lead to problems later in life. For instance, schizophrenia, Tourette's syndrome and autism are disorders where abnormal developmental events have been proposed to underlie aberrant communication in the adult brain. This programme of research will investigate the contribution of both intrinsic genetic instructions and extrinsic activity patterns to the development of the correct wiring of neurons in the striatum, a part of the brain essential for the planning and execution of movements. It has been observed that the striatum consists of two segregated pathways of information flow and that these pathways need to communicate with each other at a precise level for normal function. The experiments outlined in this proposal will investigate how much crosstalk exists between these two pathways and how genetic instructions and early life extrinsic inputs instruct the degree of crosstalk. Findings from this work will advance our understanding of foetal and neonatal brain development, with follow-on implications for our understanding of cellular changes that occur in common disorders of the nervous system.

Proteins are tiny nano-scale molecular machines that act as the workhorses of all living cells. They underpin crucial tasks spanning sensing and signalling, the coordination of metabolism and even the self-assembly of structural elements of the cell. Many of these functions can be tailored by the modification of the proteins involved, offering a way for a cell to diversity its behaviour. The broad applications of proteins in biological systems makes them an important target for engineering new forms of biology or harnessing biological components and functions in other areas like Material Science. Being able to synthesise and modify proteins on demand could unlock this huge potential. In this project we aim to directly tackle this challenge by creating what is termed an "orthogonal ribosome" that can synthesise proteins in parallel to a cell's native process. Importantly, our orthogonal ribosomes will be engineered to include attachment points for secondary components that are able to modify the protein being synthesised. By synthesising our proteins with orthogonal machinery, we avoid modifying native cellular proteins in a detrimental way and thus have the freedom to modify our own in diverse ways. Furthermore, by switching the modifying attachment that is present, we can easily change the type of modification made, creating a platform for programmable protein synthesis and modification. To achieve this ambitious goal, we will use newly developed experimental methods that can create vast numbers of orthogonal ribosome designs with different attachment points and assess the impact these have on the ability for the ribosome to effectively synthesise a protein. Those designs that work well will be selected and then modifying attachments precisely designed using computer models and simulation to have shapes that ensure the region involved in modification is perfectly positioned on the ribosome. Finally, we will combine the engineered orthogonal ribosomes and modifying attachments within living cells and test their ability to modifying a target protein such that it becomes localised to the edge of a cell when altered - a change we will be able to easily monitor using single-cell microscopy. This project is an attempt to develop the new methods needed to engineer the complex biological process of protein synthesis through the "augmentation" of a native biomolecular machine - the ribosome. Our flexible and modular approach using "plug-n-play" components offers the ability to rapidly alter the modifications made to a target protein without the need to build a new system from scratch, and opens opportunities for Biologists, Biological Engineers, and Material Scientists to better understand the function of proteins in their native context, precisely engineer their properties in living cells, and make use of highly modified proteins as nanoscale building blocks for new forms of sustainable, high-performance material. More broadly, our methodology also offers a path to harnessing other core cellular processes and repurposing their functionalities for novel applications in the emerging area of Engineering Biology.

This project will initiate a research programme in nanopore protein separation that is inspired by the nuclear pore complex (NPC). NPCs are complex, giant assemblies constituted from more than 400 proteins that define nanoscale pores (i.e. nanopores) ~40 nm in diameter. Each NPC spans the nuclear membrane which separates the cell nucleus and the rest of the cell. NPCs are the only conduits in and out of the cell nucleus in all eukaryotic cells and they allow only a small set of specific proteins and genetic material related to the functioning of the cell nucleus to pass through. All the other thousands of species of unrelated but similar molecules in the cell are rejected. Convenient separation of biomolecules is an enabling technology. NPC-studded nuclear membranes are effectively a highly specific and efficient molecular separation and purification membrane. They are capable of sorting through more than 1 kg of specific biomolecules in a human body per minute, far surpassing the performance of current technology. The creation of NPC-mimetic nanoporous membranes would benefit diverse biotechnology and biomedical applications, ranging from purification of protein disease markers for bedside medical diagnosis to continuous manufacturing of enzymes and protein therapeutics. Understanding the science underlying NPC function will help us achieve these applications and help us meet our 21st century challenges in healthcare and advanced manufacturing. The immediate goal of this project is to establish the design rules for enabling the basic function of the NPC - the sorting of proteins according to size using nanopores with a "virtual" size cut off and which, unlike current technology, are not clogged by random interactions with proteins. The pore size of the NPC is virtual because it has a physical diameter much larger than the size of the protein. A random protein cannot however pass through because each NPC nanopore is filled with a semi-porous polymer plug with an as yet unidentified structure that specifically repels proteins, except for those proteins specific to nuclear function. Biologists studying the NPC have proposed two leading theories to explain how the plug works: i) the "virtual gate" polymer brush model, and ii) the "selective phase" meshwork model. This project will create artificial nanopores that are decorated with synthetic polymers as simplified models to mimic these two theoretical structures. Experiments will be conducted to verify whether either of the theories is in fact feasible. The ultimate goal is to exploit these design rules for further development of the nanoporous membrane platform that incorporate increasingly advanced polymers for decorating the nanopores. This will create NPC-inspired nanoporous membranes with separation efficiency and selectivity that matches, and may eventually even surpass, native NPC function.

The Atlantic Meridional Overturning Circulation (AMOC) is a system of ocean currents that circulate water around the Atlantic Ocean. It is a vital part of the Earth's climate system, playing a significant role in regulating global climate and weather patterns. We need to Continuously observe the AMOC for several reasons: 1. Understanding Climate Change: Continuous observations of the AMOC help scientists better understand how climate change affects the ocean's circulation and heat transport. By continuously monitoring the AMOC, researchers can identify changes in its intensity, speed, and location, which can help them make more accurate predictions about future changes in the climate. 2. Improving Climate Models: Continuous observations of the AMOC help improve climate models by providing data to validate and refine model predictions. This information can help scientists make more accurate projections about the effects of climate change on various aspects of the Earth's ecosystem, such as sea levels, ocean acidity, and weather patterns. 3. Detecting Abrupt Changes: Abrupt changes in the AMOC could have significant impacts on the Earth's climate and weather patterns. Continuous monitoring of the AMOC can help scientists detect such changes early, allowing for timely intervention and mitigation strategies to be put in place. 4. Understanding Ecosystems: The AMOC plays a critical role in regulating oceanic ecosystems, and continuous observations can help researchers better understand how changes in the AMOC affect marine life, such as plankton, fish, and other organisms. 5. Predicting Extreme Weather Events: The AMOC has a significant impact on weather patterns, and continuous monitoring can help researchers make more accurate predictions about extreme weather events, such as hurricanes, floods, and droughts. Overall, continuous observations of the AMOC are essential for understanding the Earth's climate system and its impact on various aspects of our planet, including the environment, ecosystems, and human societies. By continuously observing the AMOC, we can improve our understanding of the Earth's climate system, and better predict and prepare for the effects of climate change. The AMOC has been observed at 26N between Florida and Africa since 2004. This is heavily reliant on tall moorings in the water and research ships to collect the data and replace the moorings. In this programme, we will exploit new technologies to design a fit-for-purpose sustainable AMOC observing system at substantially lower cost than at present and deliver data back via satellite. This will allow us to deploy an optimised lower-cost 26N AMOC observing system from 2027.