WHY CILIA ?
Short version - they are beautiful and not much is known about them !
Long version - Even though primary cilia were discovered many decades ago, they were for a long time pretty much neglected and even considered vestigial. That has very much changed during the last 15 years or so, when the importance of primary cilia for cell communications, correct embryo development, and tissue homeostasis in adulthood has started to be appreciated. This has happened hand in hand with revealing the connections between primary cilia defects and a number of diseases called ciliopathies. These include many fairly rare syndromes, as well as some of the "common ones" (cancer, obesity, fibrosis).
OUR CURRENT RESEARCH INTERESTS
Cilia formation and function from the perspective of distal appendages: focus on TTBK2
The molecular aspects of primary cilia formation have started to emerge relatively recently. It is now appreciated that control of the initiation of ciliogenesis resides in the components of distal appendages (CEP83, CEP89, CEP164, SCTL1, and FBF-1) and the effector protein associated with CEP164, Tau Tubulin Kinase 2 (TTBK2). While originally studied in relation to Alzheimer's disease, it is now establised that TTBK2 is absolutelly esential for ciliogenesis - no cilia are formed in cells devoid of the active kinase.
The requirement of components of distal appendages for regulation of cilia formation is now well documented. However, how exactly they do it - what molecular events they employ and control, is far less clear. To put the individual pieces of puzzle together to understad How does it work ? is one of the main tasks that keeps us busy.
Interplay between the regulations of cell cycle and ciliogenesis
Modelling the loss of ciliary function using human pluripotent stem cells
Successful treatment of human diseases calls for better understanding of their origin. Mounting evidence (animal models, patient data) supports the role for cilia and their individual components in the differentiation and development. For example, brain abnormalities are found in patients with mutated TTBK2 and other cilia-related genes.
We want to elucidate causalities between cilia defects and the key processes of embryogenesis. We are using a model of neural in vitro differentiation of human pluripotent stem cells, to assess what specific function might cilia serve at the particular cell commitment stage (undifferentiated cell, progenitor, precursor, fully differentiated cell).