TY  - JOUR
A1  - Batram, Christopher
A1  - Jones, Nivola G.
A1  - Janzen, Christian J.
A1  - Markert, Sebastian M.
A1  - Engstler, Markus
T1  - Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei
JF  - eLife
N2  - We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.
KW  - antigenic variation
KW  - expression site attenuation
KW  - developmental reprogramming
KW  - cell biology
KW  - genes and chromosomes
KW  - Trypanosoma brucei
KW  - variant surface glycoprotein (VSG)
KW  - monoallelic expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119727
SN  - 2050-084X
VL  - 3
IS  - e02324
ER  - 
TY  - JOUR
A1  - Stellamanns, Eric
A1  - Uppaluri, Sravanti
A1  - Hochstetter, Axel
A1  - Heddergott, Niko
A1  - Engstler, Markus
A1  - Pfohl, Thomas
T1  - Optical trapping reveals propulsion forces, power generation and motility efficiency of the unicellular parasites Trypanosoma brucei brucei
JF  - Scientific Reports
N2  - Unicellular parasites have developed sophisticated swimming mechanisms to survive in a wide range of environments. Cell motility of African trypanosomes, parasites responsible for fatal illness in humans and animals, is crucial both in the insect vector and the mammalian host. Using millisecond-scale imaging in a microfluidics platform along with a custom made optical trap, we are able to confine single cells to study trypanosome motility. From the trapping characteristics of the cells, we determine the propulsion force generated by cells with a single flagellum as well as of dividing trypanosomes with two fully developed flagella. Estimates of the dissipative energy and the power generation of single cells obtained from the motility patterns of the trypanosomes within the optical trap indicate that specific motility characteristics, in addition to locomotion, may be required for antibody clearance. Introducing a steerable second optical trap we could further measure the force, which is generated at the flagellar tip. Differences in the cellular structure of the trypanosomes are correlated with the trapping and motility characteristics and in consequence with their propulsion force, dissipative energy and power generation.
KW  - African Trypanosomes
KW  - components
KW  - bacteria
KW  - brain
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115348
SN  - 2045-2322
VL  - 4
IS  - 6515
ER  -