Investigating the role of social influence on diet and physical activity behaviours in pregnancy
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Principal supervisor: Dr Lou Atkinson
Associate supervisors: Prof Helen Pattison, Dr Ellinor Olander, City University of London

Despite the well-evidenced benefits for both mum and baby of a healthy diet, regular physical activity and healthy gestational weight gain, high quality trials of interventions have often failed to produce significant behaviour change and/or positive clinical outcomes. Research indicates that while women are motivated towards adopting a healthy lifestyle during pregnancy they experience significant pragmatic and psychosocial barriers to achieving this, including physical symptoms (nausea, fatigue, sleeplessness, etc.), uncertainty/worry about safety, and lack of time/opportunity (e.g. work and/or childcare commitments, financial constraints, etc.). Additionally, research suggests that there is significant social influence on women’s behaviours during pregnancy. This includes overt influence, such as advice and suggestions from friends, partners, family and colleagues. However, it also appears that there is less obvious but substantial influence via the social construction of a pregnant woman. With regard to diet and physical activity this can lead to women unconsciously building a picture of ‘good’ behaviours during pregnancy through observation of other pregnant women (in real life and through the media), often long before they have even considered becoming pregnant.

This PhD would use the COM-B model of behaviour and/or the Theoretical Domains Framework (TDF) to identify the relative influence of each proposed determinant on physical activity and diet behaviour during pregnancy. The research would additionally seek to identify the specific social constructions and implicit attitudes which act consciously and unconsciously on women’s decision making. The PhD would also seek to identify and test potential intervention strategies to address these influences. This will be a mixed methods PhD, combining evidence synthesis, qualitative, quantitative and experimental methods.   

Memory distortions and biases as consequences of, and contributors to, (un)healthy eating
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Principal supervisor: Dr Robert Nash
Associate supervisors: Dr Claire Farrow, Dr Jason Thomas

Reducing obesity—especially by promoting healthy eating and discouraging unhealthy eating – is of utmost societal importance, and one of the best predictors of people’s future eating behaviour is their prior eating behaviour. It is therefore clear that understanding the obesity crisis must in part require us to understand the role of memory; that is, how people remember their past experiences of eating. 

We already know that episodic memory plays a crucial role in eating behaviour. However, memory is not like a video-recorder that faithfully captures the past. Instead, it is malleable, and various cognitive and social processes can make memories susceptible to distortions and biases. Frequently, these distortions and biases operate in ways that serve to promote people’s positive sense of self-regard, and prevent them from believing that their prior actions have been undesirable or harmful. It is plausible, then, that eating behaviour may be influenced by systematic distortions of recollections that serve to minimise the apparent need for change. Certainly there is good empirical evidence that distorting people’s memories of eating experiences can influence their subsequent eating choices (Laney & Loftus, 2017; Robinson, Blissett & Higgs, 2012). Yet there is relatively little evidence concerning the extent to which more-routine, systematic biases of memory contribute to eating choices, and concerning the mechanisms by which this influence occurs. As a result, the potential for developing empirically grounded, theory-driven approaches to healthy eating based on experimental memory science remains an under-developed opportunity.
The overarching aims of this PhD will therefore be twofold:

1. To explore biases that shape how people remember their own consumption of healthy and unhealthy foods.
2. To explore how these biases can be promoted or prevented, to influence people’s subsequent eating decisions and intentions.

  Interpersonal neurofeedback: A new technique for the treatment of emotional dysregulation
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Principal supervisor: Dr Dan Shaw
Associate supervisor: Prof Klaus Kessler

Emotional dysregulation – the inability to control our emotions in stressful situations – is recognised increasingly as a core component of numerous clinical syndromes. For this reason, the last decade has seen a surge in efforts to identify effective forms of emotion-regulation training (Gross, 2015). One form of effective training is interpersonal emotion regulation – a technique that involves one individual (e.g., a patient) being directed by another (the ‘regulator’; e.g., a therapist) to employ certain emotion-regulation strategies in different contexts. A recent study showed that interpersonal emotion regulation is more effective than self-regulation (Levi-Gigi & Shamay-Tsoory, 2016). Importantly, however, the effectiveness of interpersonal emotion regulation relies entirely upon the regulator’s ability to predict the patient’s emotional reactions under different circumstances; and this, in turn, relies upon the patient’s accurate description of their affective states. This limits the potential efficacy of this training technique, since many clinical disorders are also characterized by an inability to label emotional feeling states (alexithymia). One way to overcome this is neurofeedback – that is, the real-time display of neural activity to provide an unambiguous representation of affectivity. Neurofeedback has been delivered successfully in the clinical setting with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG; see Sitaram et al., 2016). By combining the effectiveness of interpersonal emotion regulation and neurofeedback, this project will develop a new interpersonal neurofeedback intervention for emotional dysregulation.

Throughout the project, the student will investigate the characteristics that make for optimal interpersonal neurofeedback. Having identified the most effective setting for interpersonal emotion regulation, the student will then train regulators to use patients’ neurofeedback to guide their recommendations. With the facilities hosted by the Aston Brain Centre (ABC), the student will then perform neurofeedback experiments using fMRI and MEG.

Mental health difficulties in children and adults with autism spectrum disorder and rare genetic syndromes
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Principal supervisor: Dr Jane Waite
Associate supervisor: Prof Amanda Wood

A successful applicant would join an established research network that focuses on understanding and improving the identification and treatment of emotional distress in children and adults with neurodevelopmental disorders and associated intellectual disability. The applicant will be based at Aston University in the Psychology Department and they will have opportunity to collaborate with researchers and clinical psychologists from the Cerebra Centre for Neurodevelopmental Disorders at the University of Birmingham and Coventry University.
The PhD will focus on one of three areas:
•   Developing clinically sensitive assessment tools of emotional distress for minimally verbal children and adults with autism spectrum disorder.
•   Identifying personal characteristics and risk markers that are associated with the development of anxiety and depression in minimally verbal people with autism spectrum
•   Understanding the cognitive variables that underpin changes with age and emergent mental health problems in people with specific rare genetic conditions and associated
    intellectual disability.
Working in collaboration with charity and NHS partners, the successful candidate will carry out quantitative data collection and analysis with parents, children and adults with intellectual disabilities. The studentship will involve travel within the UK to see research participants.
Further information about the focus of the research team can be found by visiting the website developed by Dr Jane Waite and collaborators at:
Offer of this studentship will depend on successful completion of Enhanced DBS check.

Synthesis of mechanism-based inhibitors for β–lactamases
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Principal supervisor: Dr Dan Rathbone
Associate supervisor: Dr Tony Worthington

Owing to the overuse of penicillins, cephalosporins and carbapenems, β-lactam resistance has become a major public health problem. Many Gram-negative bacteria have developed or acquired a sub-set of β-lactamases known as carbapenemases that destroy a swathe of the world’s antibiotics of last resort.

This project will involve the synthesis and screening of candidate mechanism-based inhibitors of carbapenemases, with particular reference to New Delhi Metallo-beta-lactamase-1. The project will dovetail with a current Aston PhD study in which such compounds have been designed in silico. The target compounds contain the recognised lactam motif which, when ring-opened by the β-lactamase, will generate highly-reactive electrophilic species that are designed to react with any nucleophilic residue in the enzyme’s active site. Thus, processing the inhibitor will cause irreversible inhibition of the enzyme. This project has the potential to initiate the development of compounds that may be co-administered with carbapenems to allow the latter to be used effectively once more.

Investigating biomarkers for obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD)
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Principal supervisor:
Dr Alex Cheong
Associate supervisors: Prof Corinne Spickett, Dr Michael Stich (EAS) and Dr Mark Prince (EAS)

For obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD), the only biomarker currently widely used in drug trials is lung function testing, typically forced expiratory volume in 1s (FEV1). Although FEV1 is easy to obtain and reproducible, it does not inform about underlying disease activity and it does not separate out phenotypes of OSA and COPD. Furthermore a change in FEV1 is not specific to any of them and is unresponsive to some therapies that clearly improve survival (such as long-term oxygen therapy). This project will investigate the molecular mechanisms by which intermittent hypoxia occurring in OSA and COPD leads to vascular dysfunction in an endothelial cell model. Importantly, it has previously not been possible to model rapid hypoxic oscillations in vitro because only static hypoxia workstations and small oscillating hypoxia chambers are available. To tackle this important biomedical problem, we will use publicly available clinical data to programme a custom-rapid oscillatory gas controller for our existing static hypoxia workstation, which we will design and build within the project. Thus we will be able to mimic the rapid multiple hypoxic episodes occurring in OSA and COPD, and study endothelial cell responses in a variety of hypoxic conditions.

This is an exciting multidisciplinary PhD project bringing together experts in molecular biology (Dr Cheong and Prof Spickett, Life Sciences), environmental control (Dr Prince, Mechanical Engineering) and dynamic systems modelling (Dr Stich, Mathematics). You will assist in the design of new chambers for replicating respiratory disorders such as sleep apnoea and chronic obstructive pulmonary disease in the laboratory. From there, you will investigate the effect of simulated clinical stress on vascular and inflammatory dysfunctions to understand the nature of these disorders. The ideal candidate will be an enthusiastic student with an interest in systems biology.

Neuropsychological assessments in inherited metabolic  diseases:  Tracking outcomes in Phenylkutonuria (PKU)
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Principal supervisor: Dr Cristina Romani
Associate supervisor: Prof Amanda Wood

Phenylketonuria (or PKU) is a metabolic disease where a genetic mutation means that an amino acid --phenylalanine or Phe-- cannot be metabolized with disastrous consequences for brain development and brain health.  PKU has an incidence of about 1/10000 live births.   This means about 6200 people living with PKU in the UK, 74,000 in Europe.   The development of a PKU diet (since the seventies, pioneered first at the Birmingham Children’s Hospital) has enabled people with PKU to live normal lives, to go to University, obtain good jobs, get married and have children.  However, this success is not complete and does not come without costs.  Although most early-treated individuals with PKU have an IQ within the normal range, outcomes are not as good as in matched controls and there are significant impairments in some cognitive areas.  Moreover, following a PKU diet is costly, unpalatable and socially difficult.  Thus, most individuals with PKU abandon the diet after adolescence in spite of the fact that this is the first generation of early-treated individuals to reach adulthood and move towards middle-age and we do not know yet what the risks of abandoning the diet will be.  Acquiring this information is urgent to prevent a possible catastrophic deterioration in this population.

This project will: a) establish a detailed cognitive profile in PKU adolescents, identifying strength and weaknesses; b) link cognitive abilities to levels of Phe at different developmental stages; c) understand variability in the effects of high Phe levels on cognition and brain health; d) see whether there is a cognitive worsening for adolescents who have relaxed the diet; e) establish a cohort of participants for longitudinal long-term tracking. 

This project will help people with PKU and the professionals caring for them by acquiring new information about the effects of this disease on the brain and cognition.  In addition, it will provide us with fresh insights on the neurophysiological basis of cognitive abilities by establishing whether metabolic disorders particularly affect certain neurological populations with selective effects on cognitive abilities. You will join a dedicated interdisciplinary research team involving different professionals (cognitive scientists, dieticians, metabolic consultants, clinical neuropsychologists).  You will develop clinical, theoretical and research-based skills.  Candidates with backgrounds in cognition, neuropsychology and the neurosciences are particularly encouraged to apply.

Lipid nanoparticles for membrane protein target drug discovery
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Principal supervisor: Dr Alice Rothnie
Associate supervisors: Dr Alan Goddard, Prof David Poyner, Prof Roslyn Bill  

Membrane proteins, such as receptors and transporters, are essential in a plethora of physiological processes. Perturbation of their function often leads to disease. As such, membrane proteins are the target for over 50% of pharmaceuticals. Their location within the lipid bilayer has meant that the study of their structure and function still lags behind that of easier to isolate, soluble proteins; this has hindered progress in drug design and development. Traditionally detergents have been used to solubilise them from the membrane but this often disrupts protein activity and interferes with downstream analysis. Recently, we have shown that styrene maleic acid (SMA) polymers can be used in place of traditional detergents to isolate proteins directly from cell membranes, forming SMA lipid particles (SMALPs) where the proteins retain their lipid bilayer environment. The particles are small, stable, soluble and amenable to downstream techniques. Consequently they are more suitable for structural and functional studies and could be used for developing new drugs by fragment-based drug design, structure-based drug design and high throughput screening strategies. 

In this project, we will develop the polymer-based purification strategies to establish biophysical assays such as surface plasmon resonance (SPR) suitable for medium to high throughput screening. This project is a collaboration with Sygnature Discovery.

DeSOZ: Automatic Detection of Seizure Onset Zone from scalp EEG Signals in Children with MRE
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Principal supervisor: Dr Manousos Klados
Associate supervisors: Prof Stefano Seri, Dr Antonio Fratini

Many children with epilepsy seizures are proven medically resistant and respective surgery is the only remaining treatment alternative. This is performed for removing/deactivating a small portion of brain tissue, usually the Seizure Onset Zone (SOZ), which is usually detected using intracranial electroencephalographic (iEEG) recordings. iEEG monitoring, however, has its limitations, which are mainly found in its invasiveness, cost, and the limited spatial sampling.

During the last few years, high-frequency oscillations (HFOs above 80 Hz) have emerged as a new promising biomarker in pre-surgical diagnosis of epileptogenicity. Despite the findings, HFOs are not used in clinical practice, mainly for the lack of studies addressing their detection and analyses with non-invasive methods (standard or high-density EEGs).This studentship will focus on the automatic detection and localization of HFOs recorded by high density EEG from children suffering from medical refractory epilepsy.

The locus of visual perception: A study in virtual reality
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Principal supervisor: Prof Tim Meese
Associate supervisors: Prof Stephen Anderson, Prof Klaus Kessler 

Our starting point will be to develop Burbeck’s (1987) work on size discrimination. This work manipulated image size and object size independently by manipulating viewing distance. The results indicated that human observers have no perceptual access to the visual mechanisms in the primary visual cortex (i.e. they cannot be addressed in an optimal way for the task), but various methodological problems have undermined the power of this conclusion (e.g. Morgan, personal communication).

We shall overcome these problems with the benefit of VR by simulating a laboratory environment in virtual reality where we will have direct computer control of critical stimulus parameters such as (virtual) monitor distance. We shall then extend this work to test other image dimensions such as orientation and motion by embedding target patches within simulated 3D environments, breaking the link between object parameters and retinal parameters. We will then extend the research from simulations of near space (in the region of 1m to 5m) to vista space (e.g. 100m to 500m). The depth cues are different across these two spaces, and it has been suggested that vision might operate differently in these two domains because of this (Meese & Holmes, 2004). For example, it is more likely that basic retinal measures can be accessed when operating in vista space (i.e. looking at things a long way off). If this were found to be correct, then it would raise important theoretical questions about the nature of image data representation within visual cortex and how conscious access to that might be orchestrated within the brain. In the future, such work might be extended to include EEG, TMS and tES studies in VR in collaboration with Kessler. Finally, we will develop the adaptation paradigm to determine whether conventional psychophysical probes tap early retinal based metrics or higher-order image metrics, more closely related to our conscious visual perceptions.

Targeting growth factor signalling in mesenchymal stem cells to resolve tissue fibrosis
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Principal supervisor: Dr Jill Johnson
Associate supervisor: Dr Eric Hill 

Fibrosis is defined as the pathological accumulation of extracellular matrix components, also known as scar tissue. Organ fibrosis contributes to 50% of mortalities in the developed world, and with no existing treatments available, the need for novel therapeutics is at an all-time high. The proposed project aims to delineate the mechanisms by which tissue-resident mesenchymal stem cells (also known as pericytes) transform into collagen-producing myofibroblasts and contribute to fibrosis. Previous studies in the Johnson lab and by other groups have shown that the migration of pericytes to sites of chronic inflammation is a primary driver of tissue fibrosis and dysfunction in the lung, liver, and kidney.  The increased migratory capacity of pericytes under fibro-inflammatory conditions is driven by growth factor signalling, predominantly via TGF-β, although other growth factor signalling pathways also play a role. In the proposed research, using small molecule inhibitors of receptor tyrosine kinases likely to be involved in pericyte migration to sites of injury and inflammation (e.g. PDGFR, PDGFRβ, EGFR, TGF-β RI, TGF-β RII, and endoglin), we aim to interrogate the role of growth factor receptor signalling in enhancing pericyte migration in vitro, with the ultimate goal of testing these compounds in vivo in an effort to mitigate tissue fibrosis under chronic inflammatory conditions.

The proposed study involves the use of the house dust mite (HDM) exposure-driven mouse model of allergic asthma, which is currently considered the gold standard model for preclinical drug discovery studies in this field of research. The HDM model was developed by the project supervisor (Johnson et al. 2004) and has since been used in her group to assess the impact of inhaled corticosteroids (Johnson et al. 2008) and tyrosine receptor kinase antagonists (Johnson et al. 2015) on structural changes to the lung observed in chronic allergic asthma. Studies using this model are expected to aid in the discovery of novel targets for the treatment of number of human diseases associated with fibrosis.