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Dr Dan Mulvihill

School of Biosciences

 

Dan Mulvihill acquired expertise in cell cycle and cytoskeleton research during his PhD (co-supervised by Profs Iain Hagan and David Glover FRS) and subsequent postdoctoral position in the lab of Prof. Jerry Hyams, where he used fission yeast to study the function of the actin associated motor proteins, myosins. In 2003 he was awarded a BBSRC David Phillips Fellowship and established his own group at the University of Kent to continue research on these conserved molecular motor proteins. In 2012 he was awarded a 4-year Royal Society Industry fellowship to work with Cairn Research Ltd to develop rapid multi-dimensionlive cell imaging systems. Researchers within his lab are investigating the regulation and function of the actomyosin cytoskeleton in eukaryotes. To do this they use a variety of cross discipline approaches to elucidate how differences in the kinetic and physical properties of the actomyosin cytoskeleton, relate to its cellular properties to uncover cellular functions. Recent studies include discovering a novel regulatory mechanisms by which formin nucleation affects recruitment of tropomyosin (an actin regulator) and subsequently modulates myosin activity, as well as exploring how cell cycle and stress dependent phosphoregulation affects the motor activity and function of myosin motors.

Dan is a member of the Cell Biology, Cancer Targets and Therapies Group and the Kent Fungal Group.

Research Career

  • 1999 PhD Cell Biology, Universities of Dundee and Manchester.
  • 1999-2003 Postdoctoral Research Fellow Dept of Biology, UCL, London.
  • 2003 Postdoctoral Research Fellow, Max Planck Institute, Heidelberg.
  • 2003-2008 BBSRC David Phillips Research Fellow, University of Kent.
  • 2008-2010 Lecturer in Cell and Molecular Biology, University of Kent
  • 2010-2013  Senior Lecturer in Cell and Molecular Biology, University of Kent
  • 2013 - present, Reader in Cell and Molecular Biology, University of Kent

Orchid: 0000-0003-2502-5274

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Intracellular movement is a fundamental property of all cell types, with many organelles and molecules being actively transported throughout the cytoplasm by molecular motors. This lab's research focuses upon the study of the function of actin based motors (or myosins) in the fission yeast, Schizosaccharomyces pombe. This is a cylindrical unicellular fungi, which grows exclusively at its actin rich cell poles. The cell's polarised growth is regulated by the "polarisome" – a group of proteins which move upon polymerising microtubules to the cell tips, where they are deposited and affect the function of actin cytoskeleton regulators to promote polarized cell growth. While actin patch structures are seen to concentrate at growing poles of the cell, actin filaments extend throughout the cytoplasm, providing a track on which myosins can travel. Using a comprehensive repertoire of cross-disciplinary techniques this lab explores how myosins move upon these actin filaments and function within the cell.

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The fission yeast actin cytoskeleton

Actin is an essential cytoskeletal protein which is conserved in all eukaryotic organisms examined to date. It is actin's ability to polymerise into dynamic filaments which allows a cell's growth and even movement to be rapidly affected by both intra- and extra-cellular demands. Actin's ability to incorporate into polymers is modulated in response to either intra- and extra-cellular signals, thus leading to the regulation of a number of cellular processes, including cell growth. The filamentous actin can be incorporated into one of different types of polymer: cortical lattice structures, known as patches in yeasts, and actin cables (or filaments). Actin cables have been shown to play important roles in a variety of different cellular processes including cell polarity; cytokinesis; cell growth and movement; providing cortical tension; endocytosis; and acting as "pathways" along which molecular motors (myosins) can travel. Actin's functions are conserved within yeasts, and forms cables and patches which localise predominantly to regions of cell growth, facilitating the cells increase in size during interphase, or division during cytokinesis.

the fission yeast cytoskeleton

The fission yeast cytoskeleton.During mitosis the mitotic spindle,which is composed of microtubules (red) are required to segregate chromosome, while actin filaments (green) are incorporated into the Cytokinetic Actomyosin Ring (CAR). Upon cytokinesis this structure constricts, which leads to the formation of two identical daughter cells

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The fission yeast,Schizosaccharomyces pombe, is cylindrical in shape, with growth occurring in a polarised manner at the cell pole. Actin is seen to localise predominantly to actin patch structures at these growing cell poles and to actin cables throughout the cytoplasm during interphase. During mitosis actin cables exist as a major component of the cytokinetic ring, which contracts in order for a cell to divide. The integrity of these actin cables is maintained by a conserved coiled-coil protein called tropomyosin, which itself polymerises into filaments which coil around the actin cables and thereby promote the actin cable's structural integrity. A number of projects within this lab makes use of the cross-discipline approaches allowed by this experimentally tractable organism to determine the role tropomyosin plays in regulating actin cable dynamics and function and also modulate their ability to interact with myosin motor proteins.

 

 

S.pombe myosins

Molecular motors which associate with either microtubules or actin are responsible for undertaking tasks as diverse as chromosome segregation, maintenance of cell polarity, vesicle transport, and cytokinesis. Myosins are actin associated motor proteins that hydrolyse ATP to bring about a conformational change in their structure which exerts force against actin enables them to execute their functions in organisms as diverse as fungi and humans.

Myosins from the fission yeast Schizosaccharomyces pombe have been implicated in diverse roles in its life cycle. This lab focuses upon characterising enzymatic properties of these myosins and, utilising a combination of molecular cell biological techniques correlating this with these proteins' in vivo function. The former includes looking at the effect of changes in the endogenous myosins' structure on its cellular localisation and function. Genetic methods are also being used to examine how defects in myosins and myosin regulators change and affect the mechanical properties of yeast myosins during cell growth and division.

Using fission yeast as a model system allows the physical properties of all of the endogenous myosins (5 in total) from a single organism to be examined, thus giving an overall understanding of the mechanics of the actomyosin cytoskeleton within one cell. Using yeast also gives the opportunity to make use of the large variety of mutant strains, which have defects in genes encoding for cytoskeletal components and their regulators. Finally carrying out parallel biophysical and cell biological studies gives the opportunity to address questions using both in vivo and in vitro methods, allowing direct comparisons to be made between findings of these different experimental approaches.

Fission yeast cells

The fission yeast cells expressing fluorescently labeled type V myosin, Myo52. This movie shows how Myo52 moves rapidly throughout the cell to deliver its cargoes to discrete cellular locations

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Current Projects:

  1. The physical properties of the fission yeast myosins.

  2. Proteomics based analysis of the fission yeast type V myosin, Myo51.

  3. The role of tropomyosin in regulating actin filament dynamics in fission yeast.

  4. Molecular genetic analysis of the function of the fission yeast myosin V, Myo52.

Acknowledgements:

Work carried out in this lab is funded by the BBSRC, EPSRC, Royal Society, and the Wellcome Trust.

Collaborations:

Mike Geeves (Kent), Thomas Edwards (Leeds), William Lehman (Boston).

 

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Year 2

  • BI503 - Cell Biology

Year 3

  • BI600 - Final Year Projects (Module convenor)
  • BI610 - The Cell Cycle (Module convenor)
  • BI639 - Frontiers in Oncology
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  • Jennifer O'Brien (CMP-PhD student) joint with EDA
  • Holly Brooker (BBSRC-CASE PhD student)
  • Tara Eastwood (PhD student)
  • Irene Gyamfi (PhD student)
  • Laura Blackholly (MSc-R student)
  • Nyasha Manyanya (MSc-R student)
  • Ben Wilson (MSc-R student joint with SPS)

lab group

 

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Enquiries: Phone: +44 (0)1227 823743

School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ

Last Updated: 18/05/2017