Jordan Raff

Centrioles, Centrosomes and Cilia in Health and Disease

Centrioles are barrel-shaped structures that form two important cell organelles: centrosomes and cilia. These organelles play an important part in many aspects of cell organisation, and their dysfunction has been linked to a plethora of human pathologies including cancer and microcephaly (small brain). Our overarching goal is to understand how these organelles assemble and function at the molecular level, using a combination of biochemistry, genetics, live-cell imaging, computational/structural analysis and mathematical modelling.

Most cells in the human body are born with a pair of centrioles that can form two important cell organelles: cilia and centrosomes. These organelles play an important part in many aspects of cell organisation, including cell division, establishing and maintaining cell polarity, and positioning other organelles within the cell.

In dividing cells, the centrioles must duplicate once, and only once, during each round of cell division. Once duplicated, the centrioles have to be segregated equally between the two daughter cells. The centrioles do this by rapidly recruiting 100s of proteins (collectively termed pericentriolar material—PCM) around themselves to form centrosomes. The PCM contains many proteins that organise MTs, so the centrosomes form the two poles of the mitotic spindle, thus ensuring their accurate segregation into the two new daughter cells. Our overarching goal is to understand the molecular mechanisms that regulate centriole and centrosome assembly.

In the early Drosophila embryo, hundreds of centrioles and centrosomes synchronously assemble every few minutes as the embryos rapidly progress through repeated rounds of division. By combining live-cell imaging, computational analyses and mathematical modelling we have been generating quantitative descriptions of centrosome assembly with a precision that is not possible in other systems. We find that local oscillations in the levels of the key enzymes that initiate centriole and centrosome assembly are normally entrained by the CDK/Cyclin cell cycle oscillator to ensure that centrosomes assemble at the right time and place, and then grow to the right size. Our studies not only shed important light on centriole and centrosome assembly, but also potentially provide transformative new insights into how cells regulate and coordinate the biogenesis of their many organelles.

Group members

  • Jordan Raff (Group leader)
  • Isaac Wong (Postdoc)
  • Zach Wilmott (Postdoc)
  • Alan Wainman (Postdoc & Imaging facility manager)
  • Saroj Saurya (Lab manager)
  • Min Peng (Masters student)
  • Zsofi Novak (Postdoc)
  • Joaoa Monteiro (Postdoc)
  • Nada Mohamad (Postdoc)
  • Nic Liew (PhD student)
  • Poppy Holland-Kaye (PhD student)
  • Chia-Chun Chang (Postdoc)

Selected Publications

Latest news

Available student projects