Welcome to the Science page where we delve into the fascinating world of cilia dynamics. Here, you will find information about our research projects, publications, cilia around the world, and valuable resources.
Understanding Primary Cilia: The Tiny Antennas That Keep Our Cells in Check
What are
primary Cilia?
Imagine every cell in your body having a tiny antenna that helps it sense and respond to its surroundings. This is exactly what primary cilia are—small, hair-like structures that protrude from the surface of most cells in our bodies. Although they might look simple, primary cilia play a crucial role in keeping our cells functioning properly and ensuring that tissues develop and maintain their structure.
Primary cilia are microscopic, hair-like structures that extend from the surface of most vertebrate cells, like a small antenna. Unlike the cilia that help some cells move, primary cilia are immobile. They are made up of a core structure called the “axoneme,” which is a bundle of microtubules (tiny tubes made of protein) that are crucial for maintaining the cilium’s shape and function. The axoneme is anchored to the cell by a structure called the “basal body,” which originates from the cell’s centriole, a key player in cell division.
How Do Primary
Cilia Work?
Primary cilia function as sensory organelles, meaning they help cells detect signals from their environment and respond appropriately. They act as the cell’s version of an antenna that picks up signals and sends them back to the cell, which then decides how to react. For example, these signals could be in the form of chemicals, light, or mechanical forces like fluid flow.
The cilium’s surface is covered by a specialized membrane rich in specific proteins and lipids. These components are crucial for receiving and processing signals. Inside the cilium, a complex transport system called the intraflagellar transport (IFT) machinery helps shuttle proteins and other molecules to and from the ciliary tip, ensuring that the cilium remains functional and responsive to signals.
Why Are Primary
Cilia Important?
Primary cilia are essential for a wide range of cellular processes. For example, they play a key role in how cells communicate with each other during the development of tissues and organs. This communication is crucial for ensuring that tissues are properly organized and function as they should.
One of the best-known functions of primary cilia is their role in the Hedgehog signaling pathway, which is vital for embryonic development and tissue regeneration. Defects in this pathway can lead to serious developmental disorders and diseases like cancer. Cilia are also involved in sensing mechanical forces; for instance, in the kidneys, they detect fluid flow and help regulate the growth and function of kidney cells.
Cilia and Disease
When primary cilia don’t function properly, it can lead to a group of diseases known as ciliopathies. These conditions can cause a variety of symptoms, depending on which tissues are affected. For example, defects in cilia function can lead to polycystic kidney disease, where cysts form in the kidneys, or Bardet-Biedl syndrome, which can cause vision loss, obesity, and kidney dysfunction.
AIM
In this research unit we want to understand how primary cilia act as a dynamic organelles and how they serve as sensory antennas to transduce extracellular signals. These signals are crucial in regulating cell fates and functions during tissue development, maintenance, and remodeling in response to disease. The functionality of primary cilia is dependent on three critical factors:
To fully understand the role of primary cilia in tissue organization and function, it is necessary to study them not just as static structures but as dynamic entities that interact with their environment in complex ways. This includes investigating the molecular mechanisms underlying ciliary dynamics across different tissue types and understanding how these dynamics influence cellular processes and tissue integrity.
This research requires a multidisciplinary approach, combining expertise in various aspects of ciliary biology, to uncover the full extent of how primary cilia contribute to tissue organization and function.
Exploring the Dynamics of Primary Cilia
How cells assemble into tissues and maintain tissue integrity are central questions in biology. Primary cilia project from the surface of most vertebrate cells, where they sense and locally transduce extracellular signals. Primary cilia do not function as static organelles. Instead, they dynamically integrate extracellular input, thereby controlling cell fates and functions during tissue development, maintenance, and remodeling in disease.
Primary cilia function relies on i) the dynamic composition of molecules within the cilium, precisely regulated by the ciliary trafficking machinery and gating at the ciliary base, ii) the context-dependent sensing and processing of extracellular stimuli, and iii) the dynamic assembly and disassembly in a cell- and tissue-specific manner.
We hypothesize that integrating this triad of primary cilia dynamics is critical to control cellular processes during tissue organization and function. Dissecting how primary cilia dynamics govern tissue organization cannot be addressed by an individual lab but requires a collaborative research effort in a Research Unit (RU) with combined expertise covering ciliary dynamics in different tissue types.
Thus, the RU will address the common goal in a joint effort, which goes beyond what could be achieved by individual projects or investigators. Our RU consists of seven projects (P1 to P7). P1, P2, and P3 will define how the dynamics of intraciliary molecules control cell fate, morphogenesis, and tissue organization. P4 and P5 will reveal how extracellular stimuli regulate primary cilia dynamics to control cell fate and function. Finally, P6 and P7 will identify the molecular mechanisms underlying how primary cilia assembly/disassembly dynamics and the changes in ciliary signaling dynamics regulate tissue organization. Importantly, every project covers at least two levels of cilia dynamics, uses 2D cell culture and 3D organoids or in vivo animal models, and employs high-content data and specific hypotheses to gain mechanistic understanding.
The RU will also include a Mercator fellow who will provide standardized technological and quantitative procedures to analyze cilia dynamics using imaging. Our common goal is to analyze cilia dynamics across different cells and tissues and uncover common and context-specific mechanisms that regulate tissue development and function. On the long term, our combined efforts will allow to decipher the mechanisms that impair cilia dynamics in ciliopathies, and identify potential therapeutic targets.
Learn about our seven projects (P1 to P7) that investigate the dynamics of primary cilia in various tissues.
To gain a deeper understanding of how cilia function, it is essential to establish a global network that brings together experts in the field. This is why our research unit is committed to strengthening collaborations with cilia specialists worldwide. By doing so, our students will have the opportunity to benefit from the expertise of other labs, broadening their knowledge and enhancing their research experience.
