Caenorhabditis elegans: A genetic model to study anosmia (loss of olfaction) and neuronal cilia loss associated with Parkinson’s Disease

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September

• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

  Parkinson’s Disease or PD is the second fastest growing neurodegenerative disease in the UK. PD is an age-associated disease characterized by tremors, change in gait, loss of appetite and loss or reduction in the sense of smell (anosmia). Anosmia is reported in individuals with PD years to decade before motor symptoms (tremors and loss of dopaminergic neurons). Anosmia has a huge impact on the quality-of-life impacting body weight, mood and safety. Mutations in leucine rich repeat kinase lrrk2 gene or in glucocerebrosidase gene gba1 are most common in PD and both sets of people report anosmia. Congenital anosmia is associated with loss of a sensory structure, primary cilium, in the sensory neurons in the nose. Cilia loss is also seen in some of the neurons in the striatum (part of human brain linked to motor control) indicating cilia loss as a major feature of PD pathology. 

  A recent survey from Parkinson’s UK indicated that people with PD support research on anosmia so that treatments for motor and non-motor symptoms of PD could be found. 

  This PhD project is centered on obtaining mechanistic insights into anosmia and neuronal cilia loss using a genetically tractable nematode Caenorhabditis elegans. The PhD student will express mutant copy of human lrrk2 gene in C. elegans (LRRK2 PD model) and mutate neuronal glucocerebrosidase gba-4 (GBA PD model) by CRISPR/CAS9 to study effects on cilia morphology, odorant structure expression and receptor function in both models using robust assays established in the Singh laboratory. The student will also study the impact of age on cilia morphology and on neuronal gene expression to compare the two models of genetic PD. The outcome of the study will uncover mechanistic basis of cilia loss in PD and pave the way for treatment not only for anosmia but also for restoring motor symptoms. 

   

The student will acquire training in C. elegans maintenance, genome editing and transgenesis, imaging of olfactory neurons, transmission electron microscopy for cilia, chemotaxis assays, and transcript analysis by qRT-PCR. The student will be provided training in scientific writing, statistics and data management. The student will also receive mentoring support in an inclusive environment.