Written Assignment (Due Week 9)
This assignment will be inspired by our visit to the Littleton lab and will consist of a brief written critique about a primary paper about Huntington’s disease. Students will choose a paper (a list of options will be provided) and will write a brief report (no more than 1200 words).
Your assignment should include
- Introduction. Explain the major questions posed by the authors and also provide background information needed to understand the content of the paper.
- Results. Give a critical analysis of the experiments that were performed. Focus on the key experiment and identify the key control. Were any important controls missing?
- Discussion. Give your interpretation of the results of the paper. This may include any of the following: put the study in the context of current literature; discuss what is particularly novel or interesting about the study; propose follow-up experiments; discuss the authors’ interpretations of their results; discuss whether the findings warrant the conclusions.
- References.
Oral Presentation (Presented in the Final Class Meeting)
This assignment will focus on experimental design strategies in disease modeling. Below is a description of a novel gene, ATP13A2 (PARK9), which is linked to Parkinson’s disease. Students are asked to design several experiments, using a simple organism of their choice, to start investigating the function of ATP13A2 (PARK9) in vivo. Students will describe their ideas to the class in a 15-minute oral presentation and will also prepare a 1-page handout describing their proposed experiments. The format of the handout is at the student’s discretion (written and/or graphical representations are acceptable).
You should prepare 5 slides using presentation software (eg. PowerPoint): The first slide should describe which simple organism you are using and why and should give a brief overview of the 3 experiments you will be proposing. The next 3 slides should each describe one proposed experiment. Tell us what you would like to do, and state your hypothesis. Give details about your experimental design, including appropriate controls. Avoid giving overly technical details (such as mg concentrations). You should also tell us how you will evaluate the results and list some possible outcomes of the experiments. The final slide should tell us what you hope to be able to conclude from your proposed experiments.
After each presentation, there will be a brief class discussion. Following the oral presentations we will end the semester with a discussion about the course.
Description of ATP13A2 (PARK9)
Mutations in ATP13A2 (PARK9) cause an autosomal recessive form of parkinsonism called Kufor-Rakeb Syndrome (KRS). ATP13A2 is a lysosomal membrane protein of unknown function. To date, analysis of ATP13A2 function has been carried out in vitro using human fibroblasts from patients with KRS or shRNA knockdown of ATP13A2 in mouse primary neurons. These analyses showed that loss of ATP13A2 leads to impaired lysosomal degradation and a subsequent accumulation of α-synuclein and toxicity in primary cortical neurons.
You would like to establish an in vivo model to study how ATP13A2 functions and/or how loss of ATP13A2 contributes to PD pathogenesis. Using the strategies that we have discussed during the course, select one simple organism to study and suggest three experiments to begin building this model.