UKDRI Research Associate
Dementia is the greatest health challenge of our century.
To date there is no way to prevent it or even slow its progression, and there is an urgent need to fill the knowledge gap in our basic understanding of the diseases that cause it.
The UK Dementia Research Institute (UK DRI) is the biggest UK initiative driving forward research to fill this gap.
We are a globally leading multidisciplinary research institute of 700 staff investigating the spectrum of neurodegenerative disorders causing dementia, with laboratory-based research groups located at University College London, the University of Cambridge, Cardiff University, Edinburgh University, Imperial College London and King’s College London.
Researchers at the UK DRI at King’s use innovative approaches to explore the biological mechanisms involved in neurodegenerative diseases. Their goal is to defeat dementia by uncovering vital new knowledge that will lead to the design of smarter diagnostics and effective treatments. The team aim to understand the fundamental biological processes involved in dementia at a molecular level – and to use that knowledge to design new ways to diagnose and treat disease more precisely.
We are seeking to appoint a neuroscientist to the UK DRI research group of Professor Cho in the Department of Basic and Clinical Neuroscience. The primary research interest of the group involves understanding the pathophysiology and pathology of Alzheimer’s disease (AD) and various types of neurodegenerative diseases.
A central component of neurodegeneration is the weakening of synaptic connections and ultimately their elimination, which is thought to correlate with disease severity. Synapse weakening is therefore fundamental in AD pathogenesis. Evidence suggests that hyperphosphorylation of tau (pTau), Amyloid-beta and/or other pathogens lead to the functional and structural dysfunction of synapse; more specifically through the aberrant synapse weakening mechanism reducing the expression of AMPA receptors. AMPA receptors are considered a major component of excitatory synaptic transmission and have a critical role of functional and structural plasticity in neurons, which underlies cellular/molecular mechanism of learning and memory. We have shown that phosphorylation of specific tau residues is necessary to induce weakening of AMPA receptor function and confirmed that the severity of pathology is correlated with weakening of AMPA receptor in AD patient post-mortem hippocampal tissue.
The focus of this project is to explore a key question: which factors modulate the cellular and molecular mechanisms of ‘synapse weakening’ during dementia-associated pathology. Furthermore, we will explore if the protein interactomes of tau are differently regulated during disease progression in AD.
The role will involve cell/molecular biology and biochemical techniques, multiphoton and super-resolution imaging, optogenetics. Specifically, protein assay, GST-pulldown, cell culture and sub-cloning skills are essential.
This post will be offered on a fixed-term contract for 18 months
This is a full-time post - 100% full time equivalent
• Investigate research questions and develop specific research projects under guidance from the Group Leader
• Demonstrate the importance of your research in the form of intellectual property, novel techniques or findings that make a significant contribution to the field
• Publish at least one first or senior author publication in a high impact factor journal
• Disseminate research findings and promote your scientific profile at national/international conferences
• Contribute to the training and supervision of junior staff
The above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.
Skills, knowledge, and experience
1. PhD in relevant area of Neuroscience or Neurobiology
2. Knowledge of Neurodegeneration
3. Excellent technical skills in cell culture, Co-IP, western blotting, GST-pulldown, cloning/genetic manipulations
4. Experience in cell and molecular biology techniques
5. Quantitative and statistical analysis
6. Organisational skills and ability to deliver to stringent performance criteria
7. Good oral and written communication skills
8. Take a lead role in the project
9. Willingness to supervise junior members of the group
10. Ability to work independently, but also as part of a research team and with collaborators
1. Experience in advanced imaging technologies, such as super-resolution microscopy
2. Proteomic analyses
3. Organotypic brain slice culture
4. Preparation of high-quality iPSC line and maintenance
5. Published significant work in a relevant research field