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Modelování mitochondriální dynamiky
| Thesis title in Czech: | Modelování mitochondriální dynamiky |
|---|---|
| Thesis title in English: | Modeling of Mitochondrial Dynamics |
| Key words: | elasticita závislá na křivost, molekulární dynamika, interakce mezi proteinem a membránou |
| English key words: | Mathematical Modeling, Biophysics, Lipid Membranes, Mitochondria, Molecular Dynamics, Continuum Theory |
| Academic year of topic announcement: | 2023/2024 |
| Thesis type: | diploma thesis |
| Thesis language: | |
| Department: | Mathematical Institute of Charles University (32-MUUK) |
| Supervisor: | Christoph Allolio, Ph.D. |
| Author: |
| Guidelines |
| Mitochondrial fission and fusion serves to regulate the population, function and, potentially, natural selection of mitochondria[1].
In the future, our group wants to model these processes using molecular dynamics as well as continuum theory (especially Hamm-Kozlov-Helfrich theory)[2]. In this master thesis, the student will examine mitochondrial lipids, extract their continuum properties from molecular dynamics[3] and use it to create a simple continuum model of the mitochondrium. The final goal will be to model deformation and fusion by proteins, such as Opa1, in a similar vein as was accomplished for the cell-penetrating peptides[4]. However instead of direct simulation, a purely continuum model extracting protein curvature generating properties or using the proteins as scaffolding needs to be prepared. This work will be in collaboration with the Chao Lab at Harvard University and Hansong Ma in Cambridge, and if results are promising may be continued in a PhD thesis with these collaborators. The Chao lab has generated cellular cryo-ET data of cells with modulated Opa1 levels, and determined a mechanism for mitochondrial inner-membrane fusion by Opa1, using an in vitro reconstitution system[5]. The Chao Lab will support in vitro biochemical experiments to probe mechanisms underlying phenotypes observed in cells. The new tomography data sets generated will provide rich in situ detail into local membrane shape to validate modeling. |
| References |
| [1] Lieber T, Jeedigunta SP, Palozzi JM, Lehmann R, Hurd TR, Mitochondrial fragmentation drives selective removal of
deleterious mtDNA in the germline, Nature 570: 380-384, 2019 [2] Hamm, M., Kozlov, M. Elastic energy of tilt and bending of fluid membranes. Eur. Phys. J. E 3, 323–335, 2000 [3] C. Allolio*, A. Haluts, D. Harries, A local instantaneous surface method for extracting membrane elastic moduli from simulation: Comparison with other strategies, Chem. Phys., 514, 31-43 2018 [4] Allolio C, Magarkar M, Jurkiewicz P, Baxová K, Javanainen M, Mason PE, Šachl R, Cebecauer M, Hof M, Horinek M, Heinz V, Rachel R, Ziegler CM, Schröfel A, Jungwirth P, Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore, PNAS, 115 (47) 11923-11928, 2018 [5] Y. Ge, X. Shi, S. Boopathy, J. McDonald, A.W. Smith, L.H. Chao. Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane. eLife 2020 Jan 9:e50973 PMID: 31922487 |
| Preliminary scope of work |
| Please contact the PI allolio _at_ karlin.mff.cuni.cz for further details |
| Preliminary scope of work in English |
| Please contact the PI allolio _at_ karlin.mff.cuni.cz for further details |