The dynamics of quantum many-body systems is a fundamental yet notoriously difficult subject due to the nature of strong interactions between macroscopic number of constituents in the systems. Consider setting up a many-body system in a "simple" quantum state, one that does not have much non-local correlation between different subsystems. What are the fates of the system as it evolves in time? Does the system thermalize and exhibit chaotic behaviour, or does it localize and retain information of its initial state? A simple and elegant way of tackling these questions is to investigate the spectral statistics of the quantum many-body systems. A physical system can often be represented by a Hamiltonian - a matrix with a spectrum of energy levels which the system can occupy. The study of spectral statistics asks, what generic features does the correlation among the energy levels in the spectrum capture? Spectral statistics is a fundamental subject in physics due to its role as a robust diagnostic of quantum chaos, and due to universality - generic systems exhibit identical spectral statistics depending only on symmetry classes and dimensionality. In the last five years, spectral statistics has been utilized in multiple frontiers of modern physics, including the demonstration that black holes behave like random matrices in sufficiently late time; a debate concerning the existence of an important dynamical phase called the many-body localization; and the discovery of universal spectral signatures in quantum many-body chaotic systems, as described below. A recent discovery shows that the spectrum of generic quantum many-body chaotic systems has an extended region in which the spectral correlation deviates from known behaviour derived from random matrices. This region grows as the system size increases, and therefore presents a significant gap in our understanding of spectral statistics in the presence of many-body interaction. How does the existence of anomalous spectral correlation affect the scrambling of quantum information? This proposal aims to address such a question, and analytically extract novel signatures of spectral statistics and dynamics in isolated and open quantum many-body systems. Furthermore, despite its importance, spectral statistics in quantum many-body systems has not been experimentally measured, owing to the difficulties of resolving the tight spacing in the spectrum. The second aim of this fellowship is to experimentally measure, in collaboration with experimentalist partners, key signatures of spectral statistics in quantum many-body simulators in the lab for the first time. This project is especially timely, as it deepens and sharpens the understanding of the roles of many-body interaction in the information scrambling and processing in quantum systems, responding to the recent revival in quantum chaos, and to the rapid developments in quantum simulations of quantum many-body systems. Achieving these goals will deliver significant impacts in the constructions of broadly applicable analytical frameworks; in the first experimental measurement of spectral statistics in quantum many-body simulators; and in establishing new connections between communities in condensed matter, quantum information, and high energy physics.

My 7-year vision for this fellowship is to design, build and test hair-thin imaging devices that can better see diseases such as cancer in previously inaccessible areas of the body. Cancers occurring deep in the body are hard to detect due to their inaccessibility via natural orifices: ovarian cancer has a 50% 5-year survival rate while for pancreatic cancer this is just 1%. Early detection of these cancers could allow surgeons to treat or remove them before they spread, dramatically improving survival. However, early cancer is only subtly different to healthy tissue so accurate detection requires very high resolution imaging, much higher than MRI or X-rays. Imaging using light achieves this resolution but requires the camera to be very close to the tissue being examined, which is difficult for internal organs like the pancreas. In this fellowship, I am overcoming this limitation by developing a new generation of devices that take images through optical fibres: hair-thin pieces of glass that fit inside tiny needles and can be harmlessly inserted deep into the body. Progress: During the first 3 years of my fellowship I have built a team of 7 people (3 post-docs, 3 Ph.D. students, 1 intern) and led them to develop two new technologies that enable my overall vision. First, a nanotechnology technique for making tiny (<0.1mm) lenses and attaching them to tips of hair-thin optical fibres. These lenses enable our fibres to perform special types of imaging that improve contrast between healthy and diseased tissue compared to conventional imaging. Second, a new AI technique that corrects for image distortion created by the optical fibres as they bend while in use. This is analogous to 'seeing through frosted glass' by precisely reversing the scattering effect of the frosted glass surface. Together, these two technologies enabled me and my team to build a first-generation prototype and led to 10 journal publications (2 under review), 7 conference presentations and numerous invited talks (Arizona, St. Etienne, ICAMD in South Korea, Bath, Southampton, Cambridge). My reputation in the field has grown, and since 2022 I have sat on 3 committees for major conferences, sat on a group updating NHS Endoscopy guidelines, written an invited piece for Science China, China's domestic flagship Science journal, and been in working groups for the new ARIA funding agency and the Photonics21 partnership that defines Horizon Europe work programmes. To support my growing team I have attended two major leadership training courses and receive regular leadership coaching. I run regular lab-meetings and skills-focussed away days to mentor my team, and co-developed with my team a 'lab charter'. Plan for renewal: I will address two key challenges towards achieving the overall vision. First is the need to minimise false positives and false negatives to avoid cancer being missed or prevent unnecessary life-changing treatments. To do this, I will probe multiple biological features of tissue simultaneously by multiplexing several types of imaging in one fibre using the multi-layer lens technology we have developed. Second is the need for the instrument to be fast and robust for clinical usage. To address this, I will work with collaborators in Zhejiang to combine their new ultra-fast fibre characterisation technique with the new AI techniques we developed and test on ex vivo pancreas tissue. I will also prepare larger consortium-based bids (EPSRC Network, Horizon) to bring together the national and international community on ultrathin imaging and work with industry partners to accelerate clinical translation (MRC DPFS, KTP, iCASE). I will support my growing team to develop and fund their own research projects via pump-priming, or as Researcher Co-Investigators. Long term, I envisage a versatile endoscopy platform: wherever a needle can reach there will be an opportunity to perform a smart 'optical biopsy', offering unprecedented vision deep in the body.

The ability of bats to act as natural reservoir hosts of zoonotic viruses has been attributed to aspects of their innate immune systems. In particular, bats appear to detect and respond to pathogens differently compared to humans, allowing them to tolerate viruses that are harmful to other mammals. Studies to date have identified several lineage-specific mechanisms responsible for dampened immune and inflammatory responses in bats; however, these have mainly focused on a few putative reservoir species and their relatives, representing ~1% of bat species. It is therefore not known whether the vast majority of bat species (which span >60 million years of evolution) also possess immune mechanisms for tolerating viruses, and, if so, whether these might predispose them to viral infections and potential involvement in future zoonotic spillovers. We will conduct the first large-scale comparative study of bat immune adaptations by screening key innate immunity genes across hundreds of species, spanning this group's full evolutionary and ecological diversity. To test how putative molecular adaptations (amino acid changes) alter immune responses to viral infection, we will run cell-based assays, focusing on 3 key proteins (STING, NLRP3 and MyD88) that represent different effector pathways in innate immunity. Finally, we will examine whether the presence of impactful molecular adaptations in these and other loci can explain known variation in bat-virus associations.

People's Republic of China

Biosensors are a type of microdevices that are able to measure very small concentration of biological molecules or chemical substances through specific bio-binding or chemical absorption. Biosensors are extremely useful in diagnosis, fighting terrorist and prevention of pandemic disease spread. Through detection of associated molecules such as DNA and antibody-antigen, they are very promising in early diagnosis of cancers and genetic disorder. Widespread applications of thus biosensors will lead to fast and accurate diagnosis, thus preventing unnecessary mortality and saving thousands of lives. Deployment of biosensors at key public locations enables detection of disease or biological substances in time, preventing spread of diseases or biochemical attach. High quality biosensors must be very sensitive, easy to use, low cost and fast with integrated electronics. Also multi-detection of many molecules using arrays is essential for reliable diagnosis and detection. Although many technologies have been developed such as microarrays and label-free electrochemical and optical biosensors. they have various shortages: lack of sensitivity and resolution, bulky and precise control of the sample position, or a large device size and lack of scalability etc. A multi-disciplinary team from Universities of Cambridge (CU), University of Manchester (MU) and University of Bolton (BU) is formed to develop a technology platform for biochemical detection using the most advanced film bulk acoustic wave resonator (FBAR) technology. FBAR device has a structure similar to quartz crystal microbalance but with a submicrometer thick piezoelectric (PE) active layer. It consists of a thin PE-layer with electrodes on both sides. Application of A.C. signals generates a standing wave between the two electrodes through PE effect. The resonant frequency is extremely sensitive to mass attached on the electrode surface owing to small device dimensions (thus the small base mass) and high operating frequency. Extremely small concentration of biomolecules can be detected through specific bio-binding with pre-deposited probe molecules on the electrode surface. The device has the combined merits of all other biosensors: label-free, ultra-high sensitivity and low detection limit, small dimensions, suitability for multi-detection using FBAR arrays, electronic output signal and low cost. The project will initially focus on development of high performance FBARs using piezoelectric (PE) ZnO thin films owing to its relatively mature technology. Biosensing technology will be developed in parallel using prostate-specific antigens (PSA) and peptide aptamers that specifically bind to those PSAs. Peptide aptamers have much better stability and specificity than proteins. Development of ZnO-based FBAR biosensors enables us to clarify all issues in device modelling, fabrication and characterisation, immobilization and biodetection etc. At the second stage, the project will develop novel FBARs on glass and plastic substrates using low cost PE-polymers. PE polymers such as polyvinylidene fluoride (PVDF) and its copolymer PVDF/TrFE have a piezoelectric constant and coupling coefficient comparable to the piezoelectric ceramics, and are biocompatible and chemically inert. Owing to their flexibility, it allows fabrication on low cost glass and plastic substrates. The cost of these biosensors will be extremely low. BU has excellent facilities for modelling and design, and for material and device characterisation. They will be responsible for modelling, design and characterisation. CU has a world-class cleanroom housed with excellent deposition, etch and microfabrication facilities. They will offer the expertise and experiences in device fabrication. The MU has first class biolab environment and relevant facilities for biological research. They are experts in protein adsorption, interfacial conformation, structural unfolding, and synthesis and cloning of peptide aptamers.