PhD study

Neuroscience student in SITraN 32683

Current opportunities

Identification of the pathological changes that affect neural activity in motor neurone disease

In this project you will first collect data from healthy and patient-derived astrocyte and neuron co-cultures, for example by performing patch clamp recordings on motor neurons. Next, you will compare these recordings with computational models of healthy and pathological neurons, and identify which changes in the ion channel composition may explain the experimental data.

Analysis of RNAseH2a function in neurodegeneration

Poor DNA repair and genome instability are not only involved in cancer, but also implicated in neurodegenerative diseases. DNA damage may also be at the basis of age-related neural cell loss. In vivo models are essential to understand diseases like neurodegeneration because they result from highly complex cell and tissue interactions.

Uncovering the mechanisms leading to reduced extracellular vesicle production and secretion in C9orf72-related MND pathology

Applications are being invited for a 3.5-year basic neuroscience PhD studentship, starting in October 2019. The successful candidate will join an established training programme in the Sheffield Neuroscience Institute in the laboratories of Dr Laura Ferraiuolo and Dr Elizabeth Seward.

The role of HNRNPU in neurological disease

This project involves a collaboration between active clinicians and basic scientists. You will be working towards understanding the molecular basis for this disorder and eventually identifying routes for therapeutic intervention.

Restoring auditory function in mammals using AAV–based gene therapy

Age-related hearing loss (ARHL), which causes the progressive loss of hearing sensitivity, is the most common sensory deficit in elderly, leading to their social isolation and depression. Addressing this project will require the student to perform state-of-the-art techniques in neuroscience, such as in vivo gene therapy, in vivo and in vitro electrophysiology, immunolabeling and confocal imaging, and electron microscopy.

Memory consolidation and forgetting in natural and artificial neural circuits

What should intelligent systems do with learned information? Biological brains have evolved to retain important information as consolidated memories, while forgetting unimportant or obsolete memories. In contrast, artificial neural networks often undergo so-called ‘catastrophic forgetting’ when learning new information rather than selectively erasing irrelevant memories. Solutions to this engineering problem may find inspiration in how biological brains consolidate and forget memories.

Identification of biochemical changes linked to age-related hearing loss and their association with neurological disorders

The aim of this PhD project is to identify crucial mechanisms leading to age-related hearing loss (ARHL) by investigating mitochondrial function, DNA damage and Ca 2+ homeostasis in the auditory organ during aging. Our overarching hypothesis is that progressive accumulation of transcription-blocking DNA breaks play a key role in the development of ARHL.

Combining in vivo models and bioinformatics to investigate the role of retroelements in neuroinflammation

This research project will focus on a group of rare neurological disorders presenting with white matter abnormalities called leukodystrophies. Debilitating and fatal, they represent a unmet clinical need as there are currently very few treatments available due to lack of understanding in the mechanisms of pathology.

Neuronal activity in zebrafish models of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)

Our understanding of the genetic basis of neurodegeneration is advancing at an ever-increasing rate. One of the biggest challenges is to understand how mutations in dozens of different genes can cause the same disease in man. It seems likely that genetic mutations converge on a number of shared disease pathways, and in this project, you will test the hypothesis that defective autophagy is likely to be one such pathway in ALS/FTD.

Machine learning prediction of neurodegenerative therapy response using molecular biomarkers

The failure rate for new drugs entering clinical trials is in excess of 90 per cent, with more than a quarter of drugs failing due to lack of efficiency. In order for there to be good efficacy in clinical trials, there should be good evidence of efficacy in preclinical drug tests.

Dysregulation of calcium homeostasis

Applications are being invited for a 3.5-year basic neuroscience PhD studentship, starting in October 2019. The successful candidate will join an established training programme in the Sheffield Neuroscience Institute in the laboratories of Dr Kurt De Vos and Dr Elizabeth Seward.

What is the impact of atypical neurogenesis on brain activity, cognition and behaviour?

Neurogenesis is the process by which stem cells form brain cells. This process is disrupted by genetic mutations causing childhood neurological disorders which cause symptoms such as learning disability, behaviour problems and epilepsy. We have identified two novel genetic causes of childhood neurological disorders due to mutations in transcription factors (SOX11, MYT1L) which lead to reduced neurogenesis. These children have learning difficulties, but their symptoms have not been properly studied. There are also other childhood neurological conditions due to mutations which cause increased neurogenesis (mutations in CHD8). In this project we will identify in detail the learning and neurological problems in both these groups using detailed psychological tests.

Identification of genetic and protein modifications linked with neuropathic and inflammatory pain

This study will use human neuromas and tooth pulps available at the University of Sheffield to identify modifications of cellular and extracellular components, including extracellular vesicles, that are linked with the development of neuropathic and inflammatory pain. The project will extend our previous work that has utilised these tissues to identify proteins and miRNAs whose expression is explicitly linked with the presence and intensity of pain in man. The study will initially focus on investigating expression of a range of molecules predicted to be downstream targets of the neuropathic pain-associated miRNAs we have recently identified.

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