Pathway Simulation

Saving research time.

• Get your data faster.

• Less negative data.

• Generate preliminary data for grants.

• Increase quality of future laboratory experiments.

*Time based on a n=6/group and 2 groups. SEED experiments performed using modification of pre-curated Models.

Background: LRRK2 and Parkinson's Disease (PD)

• Genetic mutations in LRRK2 are the most common known cause of PD.
• Mutant Lrrk2 protein interacts with over 60 other biochemical entities, causing a cascade of abnormalities.
• The affected pathways include autophagy, mitochondria, neurite outgrowth, and intracellular trafficking.

We are using SEED pathway simulation to:

1. Use existing data from published original manuscripts and online databases to build a Lrrk2-specific model.
2. Manipulate the expresion and function of Lrrk2 to create in silico models of PD.
3. Identify therapeutic targets downstream of Lrrk2 that can reverse the abnormalities observed in the above models.
4. We will validate the results of these in silico findings in vivo using LRRK2 G2019S transgenics.

Findings from these studies will be exploited to develop novel therapies for LRRK2-mediated PD that may also extend to sporadic forms of PD.

Image via Protein Data Bank

Image via Protein Data Bank

Background: GBA and Parkinson's Disease (PD)

• Mutations within GBA are strong risk factors for PD.
• These mutations provide clues into the mechanisms by which the GCase enzyme (encoded by GBA) and lysosomal dysfunction relate to PD etiology.

We are using SEED pathway simulation to:

1. Use existing data from published original manuscripts and online databases to build a GBA-specific model.
2. Manipulate the expression and function of GCase in the lysosome to create in sililco models of PD.
3. Identify therapeutic targets within the sphingolipid metabolism pathway that can reverse the abnormalities observed in the above models.
4. Look for converging pathways between this model and the LRRK2-mediated model (see above).

Elucidating therapeutic targets within the sphingolipid system could impact multiple diseases, including PD, Gaucher's disease, GM1 gangliosidosis or Tay Sachs disease.