Associate ProfessorEleanor Drummond

Student Opportunities:PhD, Masters, and Honours and Dalyell projects are all currently available – please email if interested.

Project 1: Identifying Protein Drivers of Early Alzheimer’s disease

Aim: To identify the initiating protein changes that occur in human Alzheimer’s disease brain tissue.

Knowledge Gap: The earliest protein changes in Alzheimer’s disease are still unknown. This is a significant knowledge gap as these protein changes are likely initiators of disease and excellent drug targets. Through our recent proteomics studies, we have identified multiple protein changes that we hypothesize to be some of the first protein changes that occur in Alzheimer’s disease. However, we don’t yet know what these early protein changes do in the brain, whether they are cell type specific, or whether they colocalize with pathology. This project will use a combination of proteomics, multiplexed immunohistochemistry and mechanistic cell culture/in vitro studies to determine the role of these early protein changes in Alzheimer’s disease. This study will also provide key new information about whether these protein changes have potential as new therapeutic targets for Alzheimer’s disease.

Specific Research Objectives:

1. Determine how these early protein changes in Alzheimer’s disease are mislocalized in human brain tissue

2. Determine if these early protein changes promote the development of neuropathology in Alzheimer’s disease

3. Determine if these early protein changes are mechanistically involved in the development of Alzheimer’s disease

Project 2: Developing human cell models of sporadic Alzheimer's disease and primary tauopathies

Aim: To develop a new iPSC-derived human cell model that expresses neuropathology observed in sporadic Alzheimer's disease and primary tauopathies. 

Knowledge Gap: A critical limitation that has slowed drug development progress for Alzheimer’s disease and primary tauopathies has been the lack of cell models that express the complex pathology observed in the human brain. Our preliminary data suggests that seeding human cells in culture with human brain-derived proteins that accumulate in neuropathology in these diseases (e.g. beta amyloid and tau) is an attractive way to recreate disease-associated neuropathology in cell culture. This project will focus on generating and characterising these novel cell models of disease and using these cell models to perform drug screening.  

Specific Research Objectives

1. Induce disease-specific beta amyloid and tau aggregates in human iPSC-derived cell models
2. Characterize the pathological consequences of beta amyloid and tau pathology induction in novel cell models
3. Assess novel mechanisms of pathology reduction in human cell models

Project 3: Identifying new mechanistic blood biomarkers of Alzheimer’s disease

Aim: To develop a new panel of brain-derived blood biomarkers that provide a mechanistic readout of pathological changes in Alzheimer’s disease.

Knowledge Gap: Blood based biomarkers have excellent potential to provide new insight into brain changes that occur throughout the progression of Alzheimer’s disease. To date, blood biomarker studies have focused on diagnostic biomarkers, predominantly Ab and pTau. Proteomic studies have suggested that there may be many other blood biomarkers of Alzheimer’s disease, each reflecting different aspects of pathology, but information about which of these directly come from the brain and what pathological protein changes they reflect is still lacking. This information is critical as these brain-derived blood biomarkers could be used to provide a non-invasive window into specific aspects of Alzheimer’s disease pathology (e.g. plaques, tangles, inflammation, metabolic changes, synaptic changes, neurodegenerative changes, blood brain barrier breakdown, cerebral amyloid angiopathy etc). Therefore, the aim of this study is to identify a new panel of biomarkers that directly reflect brain changes in Alzheimer’s disease. Mechanistic studies will be done to determine the mechanistic role of these protein changes in the brain in Alzheimer’s disease.

Specific Research Objectives:

1. To identify brain-derived blood biomarkers in Alzheimer’s disease by correlating brain and blood proteomic datasets

2. To identify a panel of potential mechanistic blood biomarkers for Alzheimer’s disease that reflect a diverse range of Alzheimer’s disease associated pathology (e.g. plaques, tangles, inflammation, mitochondrial dysfunction, synaptic loss, neurodegeneration etc) and develop high-throughput targeted assays targeting these biomarkers.

3. Identify the mechanistic involvement of these blood biomarkers in Alzheimer’s disease pathology.