Dr Jonathan Danon

Dr Jonathan Danon, Postdoctoral Research Fellow, The University of Sydney.

Jonathan received an MSci in Chemistry with Industrial Experience from the University of Bristol in 2011. He then began his PhD studies under the supervision of Professor David Leigh FRS, first at the University of Edinburgh and then at the University of Manchester. After receiving his PhD (2015), he was hired as a postdoctoral research associate in the same group. In June 2017 he relocated to Sydney to take on a postdoctoral position with Professor Michael Kassiou and Professor Mary Collins. In February 2018 he was awarded a University of Sydney Postdoctoral Fellowship in order to carry out research on his project “Drug discovery for diagnosis and treatment of frontotemporal dementia syndromes”. His research focuses on development of small molecules for use as PET radiotracers or therapeutics targeting neuroinflammation and pathological protein aggregation.

Forefront Group:

  • USYD Medicinal Chemistry and Drug Discovery Research Group

Affiliate Organisations

University of Sydney

Neurodegeneration of interest:

Frontotemporal dementia, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis

Expertise:

  • Medicinal chemistry
  • Drug discovery
  • PET tracer development

Specific Skills:

  • Synthetic organic chemistry
  • Hit-to-lead drug discovery
  • Drug development
  • Radiotracer development
  • NMR spectroscopy
  • Mass spectrometry

Projects:

Drug discovery for diagnosis and treatment of frontotemporal dementia syndromes

Project - Drug discovery for diagnosis and treatment of frontotemporal dementia syndromes

All Chief investigators and associate investigators

  • CIA: Dr Jonathan Danon
  • AIA: Prof Michael Kassiou
  • AIB: Dr Eryn Werry
  • AIC: Dr Andrew Montgomery

Research Project Abstract

Frontotemporal dementia (FTD) is a common cause of early-onset dementia, with near comparable prevalence to Alzheimer’s disease (AD) for 45–55 year-olds. Drug discovery efforts to significantly stall, halt, or reverse brain damage have struggled badly over the past 20 years. Our research focuses on 1) developing molecular tools for studying the early stages of diseases like FTD (with potential for earlier diagnosis, aiding patient recruitment) and 2) discovery of new small molecules that reduce the damaging effects of protein aggregation in the CNS.

Disease area:

FTD, Alzheimer’s, ALS

Challenges within the field

There are currently no disease-modifying treatments for neurodegenerative diseases on the market. Our research program aims to provide better information for drug discovery scientists through development of more sensitive methods for early diagnosis of such diseases. We judiciously choose novel biological targets with therapeutic potential and use a combination of computational, medicinal chemistry, and pharmacology expertise to validate their role in neurodegeneration.

Research Project Description

The ultimate goals of this project are to discover novel chemical entities that display genuine translational promise for the diagnosis and treatment of FTD and other neurodegenerative diseases. To achieve these goals, we employ a multi-pronged approach encompassing medicinal chemistry, in silico modelling, and in vitro pharmacological testing. Projects include:

  • Structure-based design of new drugs for restricting or halting the destructive effects of tau protein aggregation, either directly or through kinase activation/inhibition or chaperone manipulation
  • Design and optimisation of new drugs for reducing or resolving TDP-43 protein aggregation, either directly or through chaperone manipulation
  • Innovative discovery of sensitive and universal positron-emission tomography (PET) tracers for dissecting microglial contributions to FTD (e.g. pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes)
  • Discovery of new small molecules that inhibit damaging neuroinflammatory pathways in the brains of FTD sufferers

Research Objectives

  • Discovery and development of novel PET radiotracers targeting different phenotypes of neuroinflammation
  • Discovery of novel small molecules targeting pathological protein aggregation in neurodegenerative disease states

Key Publications from this project

Sokias, R.; Werry, E. L.; et al. Eur. J. Med. Chem. 2020, 207, 112725.