TY  - JOUR
A1  - Pasemann, Gregor
A1  - Flemming, Sven
A1  - Alonso, Sergio
A1  - Beta, Carsten
A1  - Stannat, Wilhelm
T1  - Diffusivity estimation for activator-inhibitor models
BT  - theory and application to intracellular dynamics of the actin cytoskeleton
JF  - Journal of nonlinear science
N2  - A theory for diffusivity estimation for spatially extended activator-inhibitor dynamics modeling the evolution of intracellular signaling networks is developed in the mathematical framework of stochastic reaction-diffusion systems. In order to account for model uncertainties, we extend the results for parameter estimation for semilinear stochastic partial differential equations, as developed in Pasemann and Stannat (Electron J Stat 14(1):547-579, 2020), to the problem of joint estimation of diffusivity and parametrized reaction terms. Our theoretical findings are applied to the estimation of effective diffusivity of signaling components contributing to intracellular dynamics of the actin cytoskeleton in the model organism Dictyostelium discoideum.
KW  - Parametric drift estimation
KW  - Stochastic reaction– diffusion
KW  - systems
KW  - Maximum likelihood estimation
KW  - Actin cytoskeleton dynamics
Y1  - 2021
U6  - https://doi.org/10.1007/s00332-021-09714-4
SN  - 0938-8974
SN  - 1432-1467
VL  - 31
IS  - 3
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Moldenhawer, Ted
A1  - Moreno, Eduardo
A1  - Schindler, Daniel
A1  - Flemming, Sven
A1  - Holschneider, Matthias
A1  - Huisinga, Wilhelm
A1  - Alonso, Sergio
A1  - Beta, Carsten
T1  - Spontaneous transitions between amoeboid and keratocyte-like modes of migration
JF  - Frontiers in Cell and Developmental Biology
N2  - The motility of adherent eukaryotic cells is driven by the dynamics of the actin cytoskeleton. Despite the common force-generating actin machinery, different cell types often show diverse modes of locomotion that differ in their shape dynamics, speed, and persistence of motion. Recently, experiments in Dictyostelium discoideum have revealed that different motility modes can be induced in this model organism, depending on genetic modifications, developmental conditions, and synthetic changes of intracellular signaling. Here, we report experimental evidence that in a mutated D. discoideum cell line with increased Ras activity, switches between two distinct migratory modes, the amoeboid and fan-shaped type of locomotion, can even spontaneously occur within the same cell. We observed and characterized repeated and reversible switchings between the two modes of locomotion, suggesting that they are distinct behavioral traits that coexist within the same cell. We adapted an established phenomenological motility model that combines a reaction-diffusion system for the intracellular dynamics with a dynamic phase field to account for our experimental findings.
KW  - cell migration
KW  - amoeboid motility
KW  - keratocytle-like motility
KW  - modes of
KW  - migration
KW  - D. discoideum
KW  - actin dynamics
Y1  - 2022
U6  - https://doi.org/10.3389/fcell.2022.898351
SN  - 2296-634X
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Jonscher, Ernst
A1  - Flemming, Sven
A1  - Schmitt, Marius
A1  - Sabitzki, Ricarda
A1  - Reichard, Nick
A1  - Birnbaum, Jakob
A1  - Bergmann, Bärbel
A1  - Höhn, Katharina
A1  - Spielmann, Tobias
T1  - PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage Parasites
JF  - Cell host & microbe
N2  - During development in human erythrocytes, the malaria parasite Plasmodium falciparum internalizes a large part of the cellular content of the host cell. The internalized cytosol, consisting largely of hemoglobin, is transported to the parasite’s food vacuole where it is degraded, providing nutrients and space for growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but the parasite proteins mediating this process remain obscure. Here, we identify P. falciparum VPS45 as an essential factor in HCCU. Conditional inactivation of PfVPS45 led to an accumulation of host cell cytosol-filled vesicles within the parasite and inhibited the delivery of hemoglobin to the parasite's digestive vacuole, resulting in arrested parasite growth. A proportion of these HCCU vesicle intermediates was positive for phosphatidylinositol 3-phosphate, suggesting endosomal characteristics. Thus PfVPS45 provides insight into the elusive machinery of the ingestion pathway in a parasite that contains an endolysosomal system heavily repurposed for protein secretion.
Y1  - 2018
U6  - https://doi.org/10.1016/j.chom.2018.11.010
SN  - 1931-3128
SN  - 1934-6069
VL  - 25
IS  - 1
SP  - 166
EP  - 173
PB  - Cell Press
CY  - Cambridge
ER  -