Ilse's research relates to deconstructing the molecular signalling, 'type' specific neuronal (focusing particularly on acetylcholine-producing - so-called cholinergic neurons) and related circuitry therapeutic targets of neurodegenerative diseases, with particular emphasis on Parkinson’s disease (PD) and Lewy Body Dementia (LBD), but also holding several collaborations with Alzheimer’s disease (AD) researchers. Research in her lab encompasses three main themes:
(1) Ilse's lab has been instrumental in characterizing innovative, clinically relevant animal models of PD. To such models of disease, she applies in vivo neuromodulation using Designer Receptors Exclusively Activated by Designer Ligands (DREADDs), encompassing viral vector-mediated targeting for activating/inhibiting signaling activity of genetically-defined cells (encompassing specific neurochemical cell ‘types’). As engineered G-protein coupled receptors (GPCRs), DREADDs precisely control three major GPCR signaling pathways (Gq, Gi, and Gs) in vivo. DREADDs hold immense translational promise, due to their non-invasiveness, DREADD ligands’ high brain penetration and precision medicine ability. The design space for neuromodulation technology remains unbounded as we lack a clear understanding of which neural elements to target for improving each symptom. Ultimately, the aim of Ilse's research is to develop new types of cell- and pathway-specific stimulation strategies that are GPCR-based, thereby developing and refining neural interface technologies to improve the quality of life for people with neurodegenerative disease.
(2) On the theme of developing compounds capable of restoring neurodegenerative disease-induced aberrant cellular metabolism, Ilse collaborates extensively with medicinal chemists at UK and international universities, to evaluate the ability of novel and repurposed compounds, for example to reduce pathological iron levels and hence decrease mitochondria-derived oxidative stress. Specifically, elevated brain iron is believed to cause (or greatly contribute) to neuronal loss in age-related neurodegeneration. Ilse collaborates with various organic chemists who design novel iron chelators capable of avoiding common-side effects associated with clinically available iron chelators and apply innovative methods to allow compounds to cross the blood-brain barrier in therapeutic sufficient concentrations.
(3) A further theme in Ilse's research is understanding how, at single cell resolution, the mitochondrial genome is affected by neurodegenerative disease, for identifying novel drug targets. In particular, she interrogates mitochondrial contributions towards rendering certain brain cell-types vulnerable to age-related disease, whilst sparing others. For this, her lab applies specialist single cell mitochondrial genetic assays (e.g. mitochondrial copy number) and mitochondrial whole-genome sequencing platforms, to identify molecular-genetic clues from human post-mortem brain samples.
Ilse is currently Co-Investigator on a £300k+ British Heart Foundation project - Investigating a novel mechanism underlying increased risk of vascular events in Parkinson’s disease: Dissecting pathological synergy between protein aggregates and glycosaminoglycans (PG/22/11143).