1. Focus of research group (I)
Name PI: Deli Zhang
Department, UMC: Physiology (VUmc location)
Size of research group: 2 (Jin Li and me), under supervision of Prof. B. Brundel.
(Inter)national collaboration :
Prof. N de Groot from Erasmus MC, Rotterdam (AF Biobank)
Prof. MA Esteban from GIBH, Chinese Acedemy of Sience
Current mission, vision and aims
To uncover the molecular mechanism underlying progression of atrial fibrillation (AF): focus on Microtubule mediated SR-Mitochondria contacts (Microtubule -SMCs pathway)
To develop curable drug treatment for AF
To discover novel biomakers for AF for safer personalized treatment

2. Key role of Microtubule -SMCs pathway in AF
Normal
HDAC6
Risk factors & AF
AF onset and progression
Tubacin
SMCs tethers
GGA
Taxol
βOHB
Glutamine
So far, various high impact papers already proved that microtubules are essential for an efficient communication between the sarcoplasmic reticulum and mitochondria to conserve NADH and ATP levels, which are required for proper contractile function. I propose that disruption of the microtubule network by AF risk factors and/or AF itself results in reduction in SR and mitochondrial communication, and consequently mitochondrial dysfunction, and contractile dysfunction. Thus, preservation of the microtubule-SR and mitochondrial conacts with various drugs (fly in drugs) is a key target to prevent AF onset and progression.
Zhang et al, JMCC (2011), Zhang et al, Circulation (2014); Phillips& Voeltz, Nature (2016); Pekkurnz et al, Cell (2014)

3. Focus of research group (II)
Current expertise:
In vitro cellular model for AF
HL-1 cardiomyocytes
Adult rat atrial cells
In vivo Drosophila model for AF
Molecular biology techniques: Biochemical and Imaging
Current funding: Dr. Dekker Junior postdoc Grant from DHF

4. (s) In vivo: Tachypaced Drosophila prepupa M-mode cardiography CTL TP
Heart wall traces
(s)
As an in vivo model I will use the tachypaced Drosophila model. Why ? Since I can easily use them for genetic manipulations specifically in the heart and I successfully used them for drug screening. In Drosophila pupea the heart is present in the abdomen (point to pupa). The heart wall contractions are easily visualized with light microscopy (movie). Heart wall function can be measured by M-mode cardiography and tracers are used to measure the arrhythmicity index.
Zhang et al, JMCC (2011); Zhang et al, Circulation (2014); Den Hoed M, Brundel B. et al, Nature Genetics (2013)

5. Future plans Short term (1-2 year) plan Long term (>2 year) plan
Plan: Finish the project
Necessary infrastructure: listed in the table above
Long term (>2 year) plan
Plan: attract new funding for follow-up studies
Collaboration in ACS
Prof. J. van der Velden on the setup to measure sarcomeric contraction force (atria from patients and rats)
Prof. W. Paulus on the ZSF1 rat model
R.J.P. Musters/Imaging center on the super resolution microscopy Looking for future collaboration on Mitochondrial function measurement. (Dr. Riekelt Houtkooper …)