Difference between revisions of "Neuroenergetics: Importance of transport for the regulation of energy substrate fluxes in brain cells"
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(Project in [[Course: "Solving Biological Problems that require Math"]]) | (Project in [[Course: "Solving Biological Problems that require Math"]]) | ||
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Revision as of 21:39, 17 May 2009
Description
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.
Supervisors: Luc Pellerin & Aitana Morton de Lachapelle
Students: Elita Idrizi, Céline Pattaroni & Jennifer Tscherrig
Reference: <biblio>#barros pmid=15749163</biblio>
Outline
1st meeting: Fr. 27/2/09 (Luc Pellerin & Aitana Morton de Lachapelle)
- Biological introduction + literature to read. Discussion of the goals of the project.
Media:Neuro_notes_articles.jpg
2nd meeting: Fr. 6/3/09 (Luc Pellerin & Aitana Morton de Lachapelle)
- 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.
Media:Neuro_Intro0.jpg Media:Neuro_intro1.jpg Media:Neuro_Intro2.jpg Media:Neuro_Intro3.jpg
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.
Media:Neuro_gluc_transp1.JPG Media:Neuro_gluc_transp2.jpg
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.
5th meeting: Fr. 27/3/09 (Luc Pellerin & Aitana Morton de Lachapelle)
- Discussion of the paper by Barros et al. barros.
- 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.
Media:Neuro_Barros0.pdf Media:Neuro_Barros1.pdf
6th meeting - Midterm presentation: Fr. 3/4/09 Media:Neuroenergetics_midterm_presentation.ppt
7th meeting - Thur. 23/4/09 (Luc Pellerin & Aitana Morton de Lachapelle)
- 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.
9th & 10th meeting - Thur. 7/5/09 (Luc Pellerin & Aitana Morton de Lachapelle)
- Discussion to set up the lactate model we will consider and simulate.
- Simulations and rate-limiting factors.
Media:Notes_lactate_1.jpg Media:Notes_lactate_2.jpg Media:Equations_différentielles_lactate.jpg
(Project in Course: "Solving Biological Problems that require Math")
