Patrik Verstreken Lab

Research focus

​How does the nervous system transmit electrical pulses between neurons, and how is this process affected in neuronal disease?

We know that neurons talk to one another using small transmitter-filled synaptic vesicles that fuse with the neuronal membrane to release neurotransmitters, activating the next cell in line. While considerable progress has been made in identifying proteins present at the synapse, the role of many of them in controlling synaptic vesicle fusion, vesicle reformation at the plasma membrane and trafficking within the nerve terminal remain poorly defined. In the laboratory of neuronal communication, we address key aspects of neuronal function by employing a genetic approach using fruit flies as a model: we screen for mutations in critical genes and reveal their function by analyzing mutant phenotypes. Given the experimental advantages, flies are an ideal system to study vesicle recycling. In particular, we combine Drosophila genetics with electrophysiology, electron microscopy and live imaging of synaptic processes. The ability to apply these assays to one single type of synapse is unique and very powerful, allowing us to propose very specific functions for the proteins studied.

As a general strategy, in the lab we employ genetic screens to identify and characterize components affecting synaptic function. In one such approach we are screening the Drosophila genome by feeding flies chemical mutagens, and we use simple electrophysiological assays to isolate genes that impact the synapse. Several of the genes identified in this screen are now under investigation, and our studies continuously reveal exciting aspects of vesicle recycling and synaptic function. Interestingly, several genes that we have identified using this approach have been linked to neurological disease, including Parkinson’s disease and Amyotrophic Lateral Sclerosis, further underscoring the central involvement of neuronal communication in neuronal disease.

Building on this experience, in a second approach to identify novel genes that play a role in synaptic transmission, we are systematically testing genes implicated in neurological disease for defects in synaptic function or development. The ability to combine human disease phenotypes with genetic screening strategies using simple assays is relatively unique, and will provide new insights into common processes that underlie neurological disease progression and synaptic transmission. Already we are seeing a convergence of our two screen approaches, where our chemical mutagenesis screen identifies mutations in neurological disease genes, and conversely our neurological disease gene screen points to novel players in synaptic function, for example Rab7. Hence, we believe that our screen approaches are synergistic and will, when combined, shed new light on mechanisms of synaptic communication in healthy and diseased neurons.

Watch the Neuron video about the work on the role of ELP3 at the synapse:



Publications

Tau association with synaptic vesicles causes presynaptic dysfunctionZhou L* Mcinnes J* Wierda K Holt M Herrmann A Jackson R Wang Y Swerts J Beyens J Miskiewicz K Vilain S Dewachter I Moechars D De Strooper B Spires-Jones T De Wit J Verstreken PNature Communications, 8, 15295, 2017* These authors contributed equally
A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic TerminalsSoukup S, Kuenen S, Vanhauwaert R, Manetsberger J, Hernandez Diaz S, Swerts J, Schoovaerts N, Vilain S, Vints K, Geens A, De Strooper B, Verstreken PNEURON, 92, 829-844, 2016
Hsc70-4 Deforms Membranes to Promote Synaptic Protein Turnover by Endosomal MicroautophagyUytterhoeven V* Lauwers E* Maes I Miskiewicz K Melo M Swerts J Kuenen S Wittocx R Corthout N Marrink S Munck S Verstreken PNEURON, 88, 735-48, 2015* These authors contributed equally
Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiencyVos M, Esposito G, Edirisinghe J, Vilain S, Haddad D, Slabbaert J, Van Meensel S, Schaap O, De Strooper B, Meganathan R, Morais Epifânio V, Verstreken PSCIENCE, 336, 1306-10, 2012
Loss of skywalker reveals synaptic endosomes as sorting stations for synaptic vesicle proteinsUytterhoeven V, Kuenen S, Kasprowicz J, Miskiewicz K, Verstreken PCELL, 145, 117-32, 2011

Job openings

News

Tau prevents synaptic transmission at early stage of neurodegeneration

19/05/2017 - Prof. Patrik Verstreken’s research team (VIB-KU Leuven) has now discovered how tau disrupts the functioning of nerve cells, even before it starts forming tangles. They immediately suggest a way to intervene in this process.

Novel insights confirm pivotal role of synapse in development of Parkinson’s disease

22/03/2017 - ​Roeland Vanhauwaert and Dr. Sandra-Fausia Soukup and colleagues from the Patrik Verstreken Lab (VIB-KU Leuven) modelled a new Parkinson mutation in fruit flies and in differentiated iPS cells from different patients.

The Synapse Series - How Patrik Verstreken’s basic research advances multiple fields

26/02/2017 - ​Patrik Verstreken (VIB-KU Leuven) specializes in brain research, with a particular focus on synapses. In various brain disorders, these junctions between nerve cells play a pivotal role.

Mitochondrial lipids as potential targets in early onset Parkinson’s disease

10/02/2017 - ​A team of researchers led by Patrik Verstreken (VIB–KU Leuven) identified an underlying mechanism in Parkinson’s disease. Using flies, mice and patient cells, the team focused on cardiolipin organelles that produce energy

Researchers reveal how neurodegenerative diseases spread through the brain

09/11/2016 - Synapses play a pivotal role in the transmission of toxic proteins. This allows neurodegenerative diseases such as Alzheimer’s to spread through the brain. This the main conclusion of new research led by Patrik Verstreken (VIB-KU Leuven).

Research uncovers a new disruption at the root of Parkinson’s disease

06/10/2016 - Leading-edge research by the team of professor Patrik Verstreken (VIB-KU Leuven) has shown for the first time that a malfunctioning stress-coping mechanism in the brain is at the root of Parkinson’s disease.

Scientists track down possible new treatment for epilepsy

26/09/2016 - Increasing the concentration of specific fats in the brain could suppress epileptic seizures. This is evident from ground-breaking research carried out by groups of Patrik Verstreken (VIB-KU Leuven) and Wim Versées (VIB-Vrije Universiteit Brussel).

VIB research presents new insights in the search for treatments for neurological diseases

18/11/2015 - A team of researchers led by professor Patrik Verstreken (VIB/KU Leuven) has exposed the fine details of a mechanism that provides more insight in the communication between neurons.

New insights could result in changes to the therapeutic strategy to combat Alzheimer’s

26/05/2015 - Scientists at VIB, KU Leuven and Janssen Pharmaceutica have demonstrated that the distribution of aggregates through the brain is facilitated by synaptic connections between brain cells.

Has a possible new lead been found in the fight against neurodegenerative diseases?

24/11/2014 - Researchers from VIB and KU Leuven have succeeded in completely suppressing neurodegeneration in fruit flies, by partially inhibiting the breakdown of 'defective' proteins in brain cells.

Over-activity of enzyme HDAC6 exacerbates symptoms of Amyotrophic Lateral Sclerosis

26/06/2014 - ​Scientists at VIB and KU Leuven have demonstrated in fruit-flies that over-activity of the enzyme HDAC6 in the nerve ends exacerbates the symptoms of the neurodegenerative condition ALS.

Patrik Verstreken to be awarded 2014 IBRO-Kemali Prize for Research

08/07/2013 - The Ninth International Prize of the IBRO-Kemali Foundation will be awarded to Patrik Verstreken of VIB and KU Leuven.

Faulty energy production in brain cells leads to disorders ranging from Parkinson’s to intellectual disability

16/05/2013 - ​Neuroscientist Patrik Verstreken of VIB (Flanders Institute for Biotechnology) and KU Leuven has shown for the first time that dysfunctional mitochondria in brain cells can lead to learning disabilities.

Fruit flies can help us for the development of improved anesthetics

20/03/2013 - General anesthetic result in a loss of consciousness and insensitivity to pain, apparently in the same manner in all animals, from invertebrates to humans.

LRRK2 control of synapse - a delicate balancing exercise

14/12/2012 - Until now, it was not clearly understood how LRRK2 regulated synaptic function necessary in the treatment of Parkinson’s. This situation has now been remedied by Samer Matta from the Bart De Strooper lab, in collaboration with the Patrik Verstreken lab.

Vitamin K2: new hope for Parkinson's patients

10/05/2012 - Patrik Verstreken, associated with VIB and KU Leuven, succeeded in undoing the effect of one of the genetic defects that leads to Parkinson's using vitamin K2.

Neuron magazine features video about work by Patrik Verstreken on role ELP3 at the synapse

08/12/2011 - In a video and a paper on the Neuron website, Patrik Verstreken and his team describe their finding that ELP3 plays a role at the synapse, acetylating Bruchpilot.

Skywalker ensures optimal communication between neurons

01/04/2011 - Patrik Verstreken (VIB/K.U.Leuven) has discovered the mechanism that ensures neurons can continue to send the right signals for long consecutive periods – a process that is disrupted in neurological diseases such as Parkinson's.

Patrik Verstreken

Patrik Verstreken

Research area(s)

Model organism(s)

Bio

​PhD: Baylor Coll. of Medicine, Houston, US, 2003
Postdoc: Howard Hughes Medical Inst., BCM, Houston, US, 2003-06
VIB Group leader since 2007
VIB Science Director since 2017

Contact Info

VIB-KU Leuven Center for Brain & Disease ResearchO&N 4, 6e verdCampus GasthuisbergHerestraat 49, bus 602 3000 LEUVENRoute description