From Computational Biology Group
Background: Brain cells were shown to rely on two energy subtrates to sustain their activity: glucose and lactate. Each of these substrates are taken up by brain cells via specific transporters and metabolized in classical biochemical pathways. The critical question remains: Between metabolism and transport, what is the limiting step for the utilization of each energy substrate under resting vs. activated condition?
Goal: The goal of the project is to determine whether transport of the main energy substrates for the brain, glucose and lactate, can become rate-limiting following an increase in cerebral activity.
Mathematical tools: The student will learn to use a mathematical software (Matlab) in order to conduct simulations from a given set of parameters and equations derived from Michaelis-Menten kinetics.
Biological or Medical aspects: The “biology supervisor” will provide background of the main aspects related to brain energy metabolism and Michaelis-Menten kinetics.
- Barros LF, Porras OH, and Bittner CX. Why glucose transport in the brain matters for PET. Trends Neurosci 2005 Mar; 28(3) 117-9. doi:10.1016/j.tins.2005.01.002 pmid:15749163.
- Biological introduction + literature to read. Discussion of the goals of the project.
- Introduction to derivatives, ordinary differential equations and analytical vs numerical resolution.
- Glucose metabolism: irreversible Michaelis-Menten kinetics.
- Graphical representation of the metabolic flux as a function of neuronal glucose, in Matlab.
3rd meeting: Fr. 13/3/09 (Aitana Morton de Lachapelle)
- Glucose transport: reversible Michaelis-Menten kinetics.
- Graphical representation of the net transport- and metabolic fluxes as a function of neuronal glucose, in Matlab.
- Discussion on whether transport and/or metabolism are rate-limiting for glucose consumption by the neurons.
4th meeting: Fr. 20/3/09 (Aitana Morton de Lachapelle)
- Exercises on Matlab to solve ordinary differential equations numerically.
- Outline of the mid-term presentation.
- Discussion of the paper by Barros et al. .
- Small visit of the Physiology Institute to have an overview of the experimental techniques used (group of Luc Pellerin)
- Preparation of the mid-term presentation.
6th meeting - Midterm presentation: Fr. 3/4/09 Media:Neuroenergetics_midterm_presentation.ppt
- Modeling of pyruvate transformation into acetyl-coA by PDHc.
8th meeting - Thur. 30/4/09 (Aitana Morton de Lachapelle)
- Modeling of lactate transport and metabolism, considering different cases and parameters.
- Discussion to set up the lactate model we will consider and simulate.
- Simulations and rate-limiting factors.
11th meeting - Final presentation - Fri. 29/5/09 Media:Neuroenergetics_final_presentation.ppt