This project focuses on Totten and Denman glaciers, East Antarctica, which are influenced by ice-shelf melting. In situ observations constraining the ocean heat content causing the melt, however, are limited. To fill this gap, the project will use Air-Launched Autonomous Micro Observer (ALAMO profilers) to telemeter back repeated hydrographic profiles near the ice-shelf fronts to complement other planned ship-based efforts in these areas. Remote sensing data will be used to provide updated and improved estimates of the melt rate for each shelf. The combined melt and oceanographic data will be used to constrain parameterized transfer functions for cavity melting in response to ocean temperature, improving on current parametrizations based on limited data. These melt functions will be used with ocean temperatures from climate models to force a basin-scale, open-source ice-flow model to determine the century-scale response for a variety of scenarios, helping to reduce uncertainty in sea level contributions from this part of Antarctica. Processes other than melt that might further alter the response will also be examined. For example, as flow speed increases, damage to ice-shelf shear margins increases, potentially introducing a positive feedback. Another potential factor is reductions in ice-shelf extent that decrease buttressing and increase ice loss. To investigate these processes, numerical experiments using varying degrees of damage and ice-shelf loss will help determine the extent to which these factors might further increase sea level. Through the air-deployment of float profilers from a sonobuoy launch tube in polar settings, a long-term impact of the project will be to raise the technology readiness of operational in-situ monitoring of the rapidly changing polar shelf seas, paving the way for a transformative expansion of observations of ocean hydrographic properties from remote areas that currently are understood poorly.

Since the discovery of Sedna in 2007, the past decade has seen the discovery of a population of distant Solar System objects (often referred to as Inner Oort cloud objects [IOCs]) on a highly eccentric orbits beyond the Kuiper belt. The very existence of these distant small bodies challenges our understanding of the Solar System. These orbits are well beyond the reach of the known giant planets and could not be scattered into their highly eccentric orbits from interactions with Neptune alone. IOCs orbit too far from the edge of the Solar System to feel the perturbing effects of passing stars or galactic tides in the present-day solar neighborhood. Some other mechanism in the Solar System current or past architecture is required to emplace these extreme Solar System minor planets on their orbits. The orbits of these distant planetoids are the fossilized record of their formation. Each of the proposed scenarios offered to explain the formation of the IOCs leaves a distinctive imprint on the members of this distant population and has profound consequences for our understanding of the Solar System's origin and evolution. The majority of the known IOCs appear to come to perihelion at similar locations on the sky, which is currently proposed to be due to the active gravitational shepherding from an unseen 9th planet at ~200 au or beyond. Although there is compelling evidence to suggest the possibility of an ice giant planet beyond Neptune, there are results from other modern-day out Solar System surveys that seem to conflict with this hypothesis. To help unravel this mystery, this New Applicant Scheme proposal seeks to study the origin and properties of this distant collection of planetesimals and what they reveal about the dynamical history and environment of the outer Solar System.

United States

Over 40% of the human body is made up of skeletal muscle, which are essential for breathing, and for movement. Skeletal muscles are composed of numerous cells called muscle fibres. Within the muscle fibres, two main proteins called myosin and actin are organised into thick and thin filaments respectively, and these filaments have highly precise, lengths. These filaments are organised into muscle sarcomeres, which are in turn organised in long linear arrays from one end of the muscle fibre to the other. The interaction of myosin with actin in each muscle sarcomere drives a small shortening of each sarcomere (known as a contraction), which is summed along the muscle fibre, to drive muscle shortening, which in turn drives movement. Genetic alterations to the genes that encode part of the myosin molecule mean that a faulty (or mutant) protein is made, and this leads to severe muscle weakness in patients, in a type of disease known as myosinopathies. We do not understand how these faulty (or mutant) myosin proteins cause skeletal muscle weakness. Our research will help us to obtain a new understanding of how faulty myosin proteins cause myosinopathies. We will be able to test how mutations affect the molecular structure of the myosin, how this affects its ability to form precisely built filaments, and how this then results in changes to muscle structure, leading to muscle weakness. Our approaches will range from investigating individual fragments of myosin to investigating the organisation and properties of myosin in intact human patient samples to enable us to obtain a deep understanding. This new knowledge will not only greatly advance our understanding of myosinopathies, but, most importantly, suggest pharmacological targets that may be exploited for effective therapeutic interventions.

Heart rhythm abnormalities (beating too fast or too slow) affect more than 2 million people per year in the UK, and the consequences are a significant clinical burden. At the most malignant end of the spectrum this can result in people dying suddenly but other patterns of heart rhythm abnormality are also a leading and underestimated cause of stroke. There are data indicating genes are important, but our knowledge is limited. Heart rhythm abnormalities can be detected as changes in electrical signals, and these are identified using an electrocardiogram (ECG), a test that shows the hearts electrical activity as line tracings on a piece of paper. Prior work has indicated that measures taken from the ECG, for example heart rate, during and after exercise are strongly associated with the risk of sudden death. We propose to study the effects of exercise on heart rhythm, and will determine the genes influencing this response, as we believe exercise will amplify inherited differences. UK Biobank is a national resource for scientific research, and it has ~ 95,000 individuals who have had an exercise ECG. In a pilot study we have derived a series of measures from the ECG taken at rest, during exercise and after exercise using custom-made methods from 85 individuals. The results indicate that we can successfully extract the exercise ECG measures we are interested in. We now wish to expand the study to everyone who has had an exercise ECG, and perform tests to assess if exercise ECG measures are inherited, and further genetic studies to discover new genes. The results from this study will provide important information on genes influencing our response to exercise and recovery that will provide new insights into mechanisms, and the project also has the potential to find new genes that we can target to develop new therapies.