The EMBO conference on Cilia 2016, ‘from fundamental biology to human disease’ was held last week over four days in Amsterdam, The Netherlands. The conference brought together ciliopathy patients, clinicians, and researchers to promote collaboration, create awareness and to discuss the latest developments in research of cilia and ciliopathies.
Cilia are microtubule-based organelles that protrude from the cell surface. There are different cilia categories including primary (non-motile) cilia and motile cilia. Primary cilia are the most common and function as sensory organelles. Motile cilia beat in a wave-like pattern and are mostly involved in generating fluid flow (Roy, 2009). Cilia defects cause ciliopathies which are diseases particularly associated with cyst formation in several organs, including kidneys (Hildebrandt et al., 2011).
BHD syndrome is considered a ciliopathy. FLCN has been shown to localise to primary and motile cilia and to regulate ciliogenesis initiation (Luijten et al. 2013). It has been shown to affect Wnt signalling and regulate mTORC1 by recruiting LKB1 to primary cilia, which leads to AMPK activation (Zhong et al. (2016). Classifying BHD as a ciliopathy and further characterising FLCN’s role in ciliogenesis may help understand the pathogenesis of BHD and to identify a treatment to prevent cyst formation.
The Cilia conference included hundreds of oral and poster presentations highlighting:
- Clinical aspects of ciliopathies – including the very common kidney manifestations, novel gene mutations that induce ciliopathies, molecular tools to resolve the spectrum of ciliopathies (Dr Hannah Mitchison), lethal ciliopathies (Dr Tania Attie-Bitach), synergic effects of mutations and mutations in Wnt-pathway genes that cause ciliopathies.
- Signalling and development – including presentations on the molecular mechanisms underlying the activity of proteins involved in the formation of cilia, the role of primary cilia in the developmental of progenitor cells, the left-right organizer (LRO) and ciliopathy proteins controlling autophagy via the mTOR pathway (Andreas Struchtrup).
- Ciliogenesis and transport – including several talks on intraflagellar transport dynamics.
- Centrioles and basal bodies – including talks on centrosome cycle, cilia assembly and polarity and on the 3D structure of basal bodies (Dr Takashi Ishikawa)
- Cilium structure and organization – including the solving of structures of the molecular machinery that shuttles and sorts the membrane-associated, lipid-modified, protein to the cilium (Dr Shehab Ismail), protein-protein interactions in the cilia and the role of post-translational modifications in cilia.
- Translational therapeutics – with presentations with several mouse models that give more insight into the pathogenesis and genetic mechanisms of ciliopathies which allow for preclinical testing of new therapies (Dr Dorien J. M. Peters) and gene therapeutic approaches to correct mutations in ciliopathies.
The conference also integrated a patient perspective with a talk from Tess Harris from the Ciliopathy Alliance sharing her top tips for patient/public involvement in research. Dr Heymut Omran and Dr Nine Knoers gave a talk about European Reference Networks for rare diseases. There was also a Meet & Greet ciliopathy patients and patient groups event to promote networking between researchers and patients.
Even though there were no specific talks or posters about BHD syndrome or FLCN, several talks were relevant for BHD research either due to the similarity of symptoms with other ciliopathies or the involvement of similar pathways such as the mTOR pathway or the Wnt signalling pathway. Ultimately, the study of BHD will certainly benefit from the very intense research effort on ciliopathies that was clear during the entire conference.
This rapidly developing field is attracting an increasing amount of interest and two other Cilia conferences are already scheduled for 2017:
Cilia & Centrosomes – Suzhou, China, April 24-28
EMBO Cilia 2017 – Copenhagen, Denmark, date TBC
- Luijten, M., Basten, S., Claessens, T., Vernooij, M., Scott, C., Janssen, R., Easton, J., Kamps, M., Vreeburg, M., Broers, J., van Geel, M., Menko, F., Harbottle, R., Nookala, R., Tee, A., Land, S., Giles, R., Coull, B., & van Steensel, M. (2013). Birt-Hogg-Dube syndrome is a novel ciliopathy Human Molecular Genetics, 22 (21), 4383-4397 DOI: 10.1093/hmg/ddt288