Description of the PhD thesis project
Project: Cells proliferate by duplicating and
segregating their chromosomes into daughter cells.
In eukaryotic cells, chromosome segregation is
accomplished by the spindle – a dynamics structure composed of microtubules
(MTs), motors, non-motor microtubule-associated proteins (MAPs), and other
The spindle size is precisely controlled by
the cell, and scales with cell size – small cells have small spindles, big
cells have big spindles. Defects in spindle assembly dynamics and spindle size
can lead to errors in chromosome segregation, which result in aneuploidy and
can give rise to developmental defects such as trisomy or diseases such as
Using the model organism fission yeast (S.
pombe), the Tran team showed that the mechanism of spindle assembly is
controlled by kinesin-5 Cut7 (Rincon et al, 2017), and spindle scaling is
controlled by kinesin-6 Klp9 (Kruger et al, 2019). Is this mechanism conserved?
The potential student will compare S. pombe to
S. japonicus, a related fission yeast. These rod-shaped yeasts have 3
similar-sized chromosomes, and ~90% of their genes are similar.
However, S. japonicus is ~10x larger by volume
than S. pombe, and has a longer spindle. Importantly, whereas S. pombe has one
kinesin-5, S. japonicus has 2 kinesin-5s. These key differences enable us to
determine which motors function in spindle assembly and size control, to reveal
potential diverse mechanisms.
Objective: The potential student will carry out
experiments to compare spindle assembly and spindle scaling in S. pombe and S.
Generally, experiments involve
constructing gene-deletion, gene-mutation, or gene-tagging with fluorescent
protein; live-cell imaging of spindle dynamics; and image analysis and Cytosim
modeling of spindle dynamics.
International, interdisciplinary &
intersectoral aspects of the project
The project has interdisciplinary and
The student will perform experimental work at
the Institut Curie supervised by Phong Tran.
Theoretical and modeling work will be done
through visits to Cambridge University supervised by Francois Nedelec.
1. Loncar A, Rincon SA, Lera Ramirez
M, Paoletti A, Tran PT (2020).
Kinesin-14 family proteins and microtubule dynamics define S. pombe mitotic and
meiotic spindle assembly, and elongation. J Cell Sci 133(11):jcs240234.
2. Loiodice I, Janson ME, Tavormina
P, Schaub S, Bhatt D, Cochran R, Czupryna J, Fu C, Tran PT (2019). Quantifying Tubulin Concentration and Microtubule
Number Throughout the Fission Yeast Cell Cycle. Biomolecules 9(3):86.
3. Krüger LK, Sanchez JL, Paoletti
A, Tran PT (2019). Kinesin-6
regulates cell-size-dependent spindle elongation velocity to keep mitosis
duration constant in fission yeast. Elife 8:e42182.
4. Lin L, Chen L, Tran PT (2017). Fission yeast
neddylation ligase Dcn1 facilitates cohesin cleavage and chromosome segregation
at anaphase. Biol Open 6, 844-849.
5. Rincon SA, Lamson A, Blackwell R,
Syrovatkina V, Fraisier V, Paoletti A, Betterton MD, Tran PT (2017). Kinesin-5-independent mitotic spindle assembly
requires the antiparallel microtubule crosslinker Ase1. Nat Commun 8, 15286.