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Mehran Ahmadlou - Neuroscience 'From Body Signals to Choice: Neural Mechanisms of Reward-based, State-dependent Decision-making'
Every day, we make choices—what to eat, whether to wait for something better, or how much risk to take. These decisions might feel rational, but they are powerfully influenced by what is happening inside our bodies. Hunger or stress, for example, can make us more impulsive, more risk-seeking, or less sensitive to the actual value of a reward. These shifts are not only part of everyday life but also play a role in mental health conditions such as addiction, depression, obsessive-compulsive disorder, and eating disorders. The brain systems that shape these processes connect deep hypothalamic regions, which monitor internal states like hunger and stress, with higher-order areas in the prefrontal cortex, which are crucial for evaluating options and making decisions. When these systems interact, the “equations” of decision-making, how strongly we care about reward size, how patiently we wait for delayed rewards, or how we respond to uncertain outcomes, can change dramatically. In this project, the Neurobehavior Lab will study how hypothalamic signals of hunger and stress alter decision-making in a multi-choice task and will investigate the neural basis. Using advanced methods in freely moving mice—including miniaturized two-photon microscopy, Neuropixels recordings, fibre photometry, and targeted manipulations with optogenetics and chemogenetics—we aim to uncover how these internal signals reshape neural representations of reward amount, delay, and uncertainty, and how these changes ultimately affect choice behaviour. This research will shed light on how body states influence behaviour and help explain why decision-making often goes awry in some of the most prevalent neuropathological conditions.
Jacinta Kalisch-Smith - Cardiac Sciences / Development & Cell Biology 'Characterising placental vascular defects in mouse and human models'
Poor placental vascular formation is a major but unappreciated cause of fetal and neonatal cardiovascular disorders including congenital heart defects, fetal growth restriction and stillbirth. A major problem in this field is that these diseases are investigated primarily at term, when the baby is born. This is despite the placental vessels forming from very early in pregnancy. This project will investigate early placental development using mouse and human models to investigate how they form, their progenitor populations, the gene programmes they use to grow and what pregnancy disorders affect them. In this project, you will use high throughput imaging and analysis techniques to create 3D models of the placental vasculature. Training in wet lab work will be provided including genotyping of mouse genetic knockouts, gene expression assays to assess RNA and protein levels, and in vivo cell culture; gene knockdowns of key transcription factors and growth factors. These assays are well established in the Kalisch-Smith laboratory and will build on recent exciting findings.
Tom Keeley – Cell Biology 'Exploring cell autonomous oxygen homeostasis'
Oxygen homeostasis is a crucial and ubiquitous function of all eukaryotic cells, operating across a wide range of time scales and oxygen levels. Whilst specialised central and peripheral mechanisms control systemic arterial oxygen levels, this cannot provide localised or regional oxygen homeostasis. Transcriptional adaptations to hypoxia orchestrated largely by the hypoxia-inducible factors does occur ubiquitously, yet cannot provide rapid homeostatic control. This project will explore the role of a more recently described oxygen sensing pathway in mediating rapid and ubiquitous oxygen homeostasis. Coordinated by 2-aminoethanethiol dioxygenase (ADO) and the Cys branch of the N-degron pathway, this pathway controls the stability of regulators of G-protein signalling 4 and 5. State-of-the art molecular biological techniques will be employed to study how these proteins interact with the subcellular environment to affect cell autonomous oxygen homeostasis, focusing on control of mitochondrial function. Analysis of protein expression and location will be paired with functional readouts of cell physiology, including measurements of intracellular oxygen levels and second messenger signalling.
Outreach: How Science Week's 2025 theme made me reflect on how I talk about science (by Dr Katherine Brimblecombe)
Science week 2025 theme: Change and adapt
Molly Stevens - Next-Generation mRNA Vaccines: Safer Delivery with Biodegradable Polymers
This project focuses on advancing mRNA vaccine delivery by exploring biodegradable polymers as an alternative to traditional lipid nanoparticles (LNPs). While LNPs, used in vaccines like Pfizer/BioNTech and Moderna, are effective for delivering mRNA into cells, their full immune impact is not yet well understood, potentially leading to adverse effects. Biodegradable polymers, on the other hand, offer greater safety and efficiency due to their ability to be easily cleared from the body and their customizable properties for improved delivery. The project aims to develop lipid-like polymeric nanoparticles (lipidoids) that combine the benefits of both polymer and lipid systems. By synthesizing and testing a wide range of nanoparticle formulations, the goal is to identify new polylipidoid particles that outperform current LNP technology in delivering mRNA to the immune cells in the skin. Success in this research could lead to the development of more effective and safer vaccines, offering better immune responses with fewer side effects. The findings will be important for combating infectious diseases and enhancing the future of vaccine technology.
Molly Stevens - Developing next-generation biosensing technologies
Point-of-care (PoC) testing is vital for managing disease outbreaks and improving healthcare access, especially in low- to middle-income countries (LMICs) where disease prevalence is high and resources are scarce. Traditional molecular diagnostics, such as PCR, require specialized equipment and skilled personnel, making them impractical for PoC settings in resource-limited areas. This project aims to advance PoC diagnostics by integrating platinum nanocatalysts (Pt@Au) into paper-based lateral flow assays (LFAs). These enhanced LFAs offer superior detection limits compared to conventional tests and provide colorimetric results that minimize user error. Additionally, they can incorporate a barcode-style system for multiplexed detection, enabling differential diagnosis across multiple diseases. The project focuses on developing next-generation multiplexed LFAs that can detect both nucleic acids and proteins simultaneously with high sensitivity. By enabling the simultaneous detection of multiple biomarkers in a single test, this project seeks to improve disease management and public health outcomes in LMICs, offering a practical and effective tool for comprehensive diagnostics in challenging settings.
Molly Stevens - Bionanoscience 'Guiding Brain Organoids: Advanced Scaffolds for Neural Growth'
The human brain and its function are one of the big mysteries of humankind. Many strategies are helping to gain a fundamental understanding of the development and function of the central nervous system: imaging of the human brain, post-mortem analysis, animal models, and – since only a few years – advanced three-dimensional neural structures which reassemble aspects of the human brain, called brain organoids. Brain organoids have been used to model brain development, diseases and neural circuit formation and function. However, to date the lack of directional control over neurogenesis, as well as the limited capability to support larger tissue structures with sufficient nutrition, limit the potential of these human stem cell derived tissues. In this project we aim to develop a scaffold to support directional neurogenesis and perfusion of large brain organoids. The student will learn a range of methodologies, which will include (but are not limited to) stem cell culture, neural differentiation, 3D printing, confocal microscopy and live imaging. Furthermore, the student will be involved in the fabrication and functionalisation of biomaterials.
Ana Domingos - Metabolism and endocrinology 'Fundamental biological mechanisms in Sympathetic Neurocircuitry underlying body weight'
Effective obesity management medications that elevate energy expenditure, such as brain-acting sympathomimetics, lead to descending widespread sympathetic activity that raises the heart rate1. These adverse cardiovascular side effects have repeatedly resulted in their market withdrawal or rejection by regulatory agencies despite their potency in reducing body weight. Consequently, treatment options have been limited to suppressing appetite, for instance, with Glucagon-like peptide-1 (GLP-1) mimetic drugs, which lead to a compensatory decrease in energy expenditure, increasing the risk of recurrent weight gain2,3. While reducing food intake is crucial for treating obesity, sustaining a higher energy expenditure is necessary for therapies to be durable. This could be achieved by directly manipulating subpopulation of sympathetic neurons as they release factors within metabolic tissues that trigger anti-obesity actions beyond appetite control4–6, and without cardiac side effects1,7.
Pawel Swietach - Cell physiology Metabolism & Endocrinology 'Break the Acid Cycle: Targeted Collapse of Tumour Adaptation'
Break the Acid Cycle: Targeted Collapse of Tumour Adaptation DPAG Supervisor: Pawel Swietach
Mootaz Salman - Neuroscience - 'Advanced 3D brain-on-a-chip platforms to study molecular mechanisms of neurodegeneration'
The brain microenvironment is tightly regulated by the blood–brain barrier (BBB) which maintains the central nervous system internal milieu. BBB leakage following neuroinflammation (or systemic inflammation) has recently been described early in the occurrence and development of neurodegenerative disorders including Parkinson’s, Alzheimer's, and cerebral small vessel disease. Dynamic 3D models of the BBB represent a major advance on traditional static 2D models allowing cells to be in a physiologically realistic native-like 3D environment that faithfully recapitulate the complexity of an in vivo system without artificial support membranes. We seek highly motivated DPhil students with either a scientific or medical background to join our group to work on the molecular mechanisms of BBB (dys)function in neurodegeneration. In this project, you will combine the use of patient-derived induced pluripotent stem cells (iPSCs) together with novel brain-on-a-chip platforms, advanced microscopy, microfluidics, and molecular assays. This project will advance our ability to understand how does inflammation-mediated BBB dysfunction lead to the development of neurodegeneration and dementia. It will establish a framework to address fundamental questions about the role of the BBB in health and neurodegeneration.
Black History Month 2023 - Saluting Our Sisters: Mary Logan Reddick
Mary Logan Reddick (31 December 1914 - 1 October 1966)
Black History Month 2023 - Saluting Our Sisters: Marie Daly
Marie Daly (April 16th, 1921 – October 28th, 2003)
Black History Month 2023 - Saluting Our Sisters: Dolores Cooper Shockley
Dolores Cooper Shockley (21 April 1930-10 October 2020)
Damian Tyler - Cardiac Sciences / Metabolism & Endocrinology - 'Assessment of Cardiac Metabolism Using Hyperpolarized Magnetic Resonance Imaging'
The role of abnormal cardiac substrate metabolism in the development of many cardiovascular diseases and the therapeutic potential of interventions targeting cardiac substrate metabolism are unclear. Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) have long been used to monitor cardiac structure and function. However, the application of MRI/MRS for metabolic imaging has been limited by an intrinsically low sensitivity. Hyperpolarized Magnetic Resonance (hp-MR) is a new technique that yields greater than 10,000-fold signal increases in MR images and enables unprecedented real-time visualization of the biochemical mechanisms of abnormal metabolism. This allows measurement of instantaneous rates of substrate uptake and enzymatic transformation in vivo, providing a sensitive assessment of disease and a new means to monitor treatment response. This project will explore the application of hp-MR in the study of cardiovascular disease, enabling the assessment of pyruvate metabolism through the key metabolic enzyme, pyruvate dehydrogenase, and how it can be modulated as a therapeutic target.