Brain diseases – different models, new insights

Speaker: 

Alexander Whitworth, PhD 

MRC Mitochondrial Biology Unit, University of Cambridge, UK 

Biography of the speaker: 

Dr Alex Whitworth is an MRC Investigator in the MRC Mitochondrial Biology Unit at the University of Cambridge. His research team is focused on understanding the underlying mechanisms of neurodegeneration and identifying potential therapeutic targets, primarily using Drosophila as a powerful in vivo model system. Following a PhD at the University of Cambridge, studying developmental genetics in Drosophila, he joined the laboratory of Prof. Leo Pallanck at the University of Washington, where he developed several new Drosophila models of Parkinson's disease, including PINK1 and Parkin. In 2005, he started his own research group at the University of Sheffield and was recruited to Cambridge in 2015. Dr. Whitworth’s group has made fundamental discoveries into the mechanism of action of the PINK1-Parkin pathway that impacts on the long-term health of the mitochondrial network and ultimately on neuronal survival. The team has also recently identified mitochondrial calcium as an important factor in PINK1/Parkin-related neurodegeneration and is investigating the intersection with the gut-brain axis. Discoveries from these investigations will help identify potential therapeutic targets to boost mitochondrial health to maintain neuronal survival.  

Description of the general focus of the symposium: 

The brain is the most complicated and vulnerable organ in the body. Physical injuries, environmental changes, pollution, and genetic mutations can result in severe dysfunctions that present with nonspecific symptoms and are difficult to classify. The limited and challenging nature of human brain research encourage to investigate various animal models. The session will be divided into two parts: the use of an alternative model, Drosophila melanogaster and mammalian models. Invited speaker Alex Whithworth is an expert in  Parkinson’s disease research.  He will introduce the audience to how to use Drosophila as a model, and he will present his data about the role of mitophagy in PD. The next two early-stage researcher speakers will follow the same model. Justyna Kadłuczka will show the  data about the effect of synuclein expression in the photoreceptor cells on the retina and brain functioning. Zuzanna Kula will present the data about the possibility of using inhibitors of glusylceramidase beta in PD treatment. The next part will be focused on mammalian models. The first speaker, Aleksandra Klachacz, will show her data about the role of astrocytic factors in the post-ischemic brain. To cover a variety of models, this talk will be followed by Chin Long Poo who will present how optimized rotenone exposure accelerated dopaminergic dysfunction and Parkinsonian behaviour in adult zebrafish.

What can we learn about Parkinson’s disease from fruit flies. 

Brief description of the talk: 

Parkinson’s disease (PD) is a common neurodegenerative movement disorder that is typically caused by a combination of genetic and environmental factors. Relatively rare inherited forms of PD have delivered incredible insights into the pathogenic mechanism and have consistently highlighted defects in proteostasis and mitochondrial dysfunction. Two genes linked to inherited PD, PINK1 and PRKN, provide the strongest links to mitochondrial dysfunction as their encoded proteins (the kinase PINK1 and ubiquitin ligase Parkin) function to signal the selective degradation of mitochondria – a process termed mitophagy. Many aspects of PINK1/Parkin function are deeply conserved through evolution. Since their development, the Drosophila models of the orthologous genes, Pink1 and parkin, have delivered fundamental insights into their physiological function. The strength of the model is due largely to the robust phenotypes of the genetic knockouts, which confer mitochondrial disruption, locomotor deficits, and neurodegeneration under basal conditions. Applying the powerful genetic tools available in Drosophila has uncovered important molecular and cellular aspects of Pink1/parkin disruption to tissue and organismal health. A key advantage of analysing Pink1/parkin function in an animal model is the ability to interrogate inter-organ, such as the gut-brain axis, as well as systemic impacts on neurodegeneration and healthspan. Here, the  latest advances of Dr. Alex Whitworth team on understanding the physiological roles of Pink1/parkin as well as the consequences of their dysfunction and therapeutic opportunities.