Professor Cheryl Woolhead

  • Professor of Molecular Biotechnology (Molecular Biosciences)
  • Dean of Postgraduate Teaching (MVLS College Senior Management)

telephone: 01413305161
email: Cheryl.Woolhead@glasgow.ac.uk

Level 4, Institute of MC&SB, Bower Building, Glasgow G12 8QQ

Import to contacts

ORCID iDhttps://orcid.org/0000-0002-4774-2840

Research interests

Our group here at Glasgow is interested in the relationship between translating ribosome and nascent polypeptide. Currently this leads us into two main avenues of research.

Membrane protein folding and insertion

Inner membrane proteins make up 20-30% of the bacterial proteome. The major route of insertion for such proteins is via the Sec machinery. However certain membrane proteins are Sec independent and instead insert via an essential membrane protein called YidC. Despite the importance of YidC, the precise function and mechanism of this protein are difficult to define. In our lab we are using Fluorescence Resonance Energy Transfer (FRET) to monitor structural changes of an inner membrane protein during synthesis on the ribosome, targeting to the YidC pathway and integration into the membrane. This technique enables us to monitor the compaction of α-helices and the formation of tertiary structure, in order to elucidate the timing of folding events that occue between the ribosome exit tunnel and the adoption of the final functional conformation in the membrane. The findings are supported by in vitro insertion assays and crosslinking to the signal recognition (SRP), which provide further details of the role of SRP in YidC targeting.


Figure 1. Structural analysis of membrane protein insertion
References:
Robinson, P. J., Findlay J. E. and Woolhead C. A. In Press (2012)
Woolhead, C. A., McCormick P. J. and Johnson A. E. Cell (2004)

Translation Arrest motifs

Although ribosomes are responsible for the synthesis of all cellular proteins it was initially believed that translating nascent chains would not interact with the exit tunnel during synthesis. However a small but increasing number of proteins have been identified which interact with the ribosome exit tunnel to induce translational arrest. Escherichia coli secretion monitor (SecM) is one such stalling peptide, SecM monitors the cell export activity through its own translocation to the periplasm and upregulates translation of SecA, an ATPase involved in the SecYEG translocation machinery, when translocation is reduced. How these peptides interact with the exit tunnel is not fully understood however two key features required for stalling include an essential peptide arrest motif and compaction of the nascent chain within the exit tunnel upon stalling. By investigating the SecM sequence found inside the ribosome tunnel and analysis of compaction of the nascent chain in the exit tunnel by structural and biochemical assays we are investigating the interactions between the nascent chain and the exit tunnel which contribute to translation arrest.


Figure 2. Nascent SecM induced translation arrest
References:
Woolhead, C. A. Johnson, A. E. and Bernstein H. D. Molecular Cell (2006)


Publications

List by: Type | Date

Jump to: 2020 | 2019 | 2018 | 2017 | 2016 | 2013 | 2012 | 2010 | 2006 | 2004 | 2003 | 2002 | 2001
Number of items: 18.

2020

Zhang, Y., Bracken, H., Woolhead, C. and Zagnoni, M. (2020) Functionalisation of human chloride intracellular ion channels in microfluidic droplet-interface-bilayers. Biosensors and Bioelectronics, 150, 111920. (doi: 10.1016/j.bios.2019.111920) (PMID:31791876)

2019

Cherry, J. K. and Woolhead, C. A. (2019) Hydrophobicity, rather than secondary structure, is essential for the SRP dependent targeting of GPR35 to the ER membrane. Journal of Bioenergetics and Biomembranes, 51(2), pp. 137-150. (doi: 10.1007/s10863-019-9785-0) (PMID:30706279) (PMCID:PMC6439181)

Bracken, H. A. and Woolhead, C. A. (2019) Increased freedom of movement in the nascent chain results in dynamic changes in the structure of the SecM arrest motif. Bioscience Reports, 39(1), BSR2018124. (doi: 10.1042/BSR20181246) (PMID:30563926) (PMCID:PMC6340945)

2018

Zagnoni, M. and Woolhead, C. (2018) Droplet-based microfluidic platform for intracellular ion channel drug discovery. Impact, 2018(7), pp. 68-70.

2017

Robinson, P. J. , Pringle, M. A. , Woolhead, C. A. and Bulleid, N. J. (2017) Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation. Journal of Biological Chemistry, 292(17), pp. 6978-6986. (doi: 10.1074/jbc.M117.780742) (PMID:28298446) (PMCID:PMC5409466)

2016

Cabrita, L. D. et al. (2016) A structural ensemble of a ribosome–nascent chain complex during cotranslational protein folding. Nature Structural and Molecular Biology, 23(4), pp. 278-285. (doi: 10.1038/nsmb.3182) (PMID:26926436)

2013

Robinson, P.J. and Woolhead, C.A. (2013) Post-translational membrane insertion of an endogenous YidC substrate. Biochimica et Biophysica Acta: Molecular Cell Research, 1833(12), pp. 2781-2788. (doi: 10.1016/j.bbamcr.2013.07.003) (PMID:23872420)

2012

Robinson, P.J. , Findlay, J.E. and Woolhead, C.A. (2012) Compaction of a prokaryotic signal-anchor transmembrane domain begins within the ribosome tunnel and is stabilized by SRP during targeting. Journal of Molecular Biology, 423(4), pp. 600-612. (doi: 10.1016/j.jmb.2012.07.023) (PMID:22867705)

2010

Peterson, J.H., Woolhead, C.A. and Bernstein, H.D. (2010) The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding. Molecular Microbiology, 78(1), pp. 203-217. (doi: 10.1111/j.1365-2958.2010.07325.x) (PMID:20804452) (PMCID:PMC2950912)

2006

Woolhead, C.A. , Johnson, A.E. and Bernstein, H.D. (2006) Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. Molecular Cell, 22(5), pp. 587-598. (doi: 10.1016/j.molcel.2006.05.021)

2004

Woolhead, C.A. , McCormick, P.J. and Johnson, A.E. (2004) Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell, 116(5), pp. 725-736. (doi: 10.1016/S0092-8674(04)00169-2)

2003

Peterson, J.H., Woolhead, C.A. and Bernstein, H.D. (2003) Basic amino acids in a distinct subset of signal peptides promote interaction with the signal recognition particle. Journal of Biological Chemistry, 278(46), pp. 46155-46162. (doi: 10.1074/jbc.M309082200)

2002

Rodger, A. et al. (2002) Flow oriented linear dichroism to probe protein orientation in membrane environments. Physical Chemistry Chemical Physics, 4, pp. 4051-4057. (doi: 10.1039/b205080n)

Tissier, C., Woolhead, C.A. and Robinson, C. (2002) Unique structural determinants in the signal peptides of 'spontaneously' inserting thylakoid membrane proteins. European Journal of Biochemistry, 269(13), pp. 3131-3141. (doi: 10.1046/j.1432-1033.2002.02943.x)

2001

Mant, A., Woolhead, C.A. , Moore, M., Henry, R. and Robinson, C. (2001) Insertion of psak into the thylakoid membrane in a 'horseshoe' conformation occurs in the absence of signal recognition particle, nucleoside triphosphates, or functional albino3. Journal of Biological Chemistry, 276(39), pp. 36200-36206. (doi: 10.1074/jbc.M102914200)

Robinson, C., Thompson, S.J. and Woolhead, C.A. (2001) Multiple pathways used for the targeting of thylakoid proteins in chloroplasts. Traffic, 2(4), pp. 245-251. (doi: 10.1034/j.1600-0854.2001.1r010.x)

Woolhead, C.A. , Mant, A., Kim, S.J., Robinson, C. and Rodger, A. (2001) Conformation of a purified 'spontaneously' inserting thylakoid membrane protein precursor in aqueous solvent and detergent micelles. Journal of Biological Chemistry, 276(18), pp. 14607-14613. (doi: 10.1074/jbc.M009600200)

Woolhead, C.A. , Thompson, S.J., Moore, M., Tissier, C., Mant, A., Rodger, A., Henry, R. and Robinson, C. (2001) Distinct albino3-dependent and -independent pathways for thylakoid membrane protein insertion. Journal of Biological Chemistry, 276(44), pp. 40841-40846. (doi: 10.1074/jbc.M106523200)

This list was generated on Thu Apr 18 10:35:24 2024 BST.
Jump to: Articles
Number of items: 18.

Articles

Zhang, Y., Bracken, H., Woolhead, C. and Zagnoni, M. (2020) Functionalisation of human chloride intracellular ion channels in microfluidic droplet-interface-bilayers. Biosensors and Bioelectronics, 150, 111920. (doi: 10.1016/j.bios.2019.111920) (PMID:31791876)

Cherry, J. K. and Woolhead, C. A. (2019) Hydrophobicity, rather than secondary structure, is essential for the SRP dependent targeting of GPR35 to the ER membrane. Journal of Bioenergetics and Biomembranes, 51(2), pp. 137-150. (doi: 10.1007/s10863-019-9785-0) (PMID:30706279) (PMCID:PMC6439181)

Bracken, H. A. and Woolhead, C. A. (2019) Increased freedom of movement in the nascent chain results in dynamic changes in the structure of the SecM arrest motif. Bioscience Reports, 39(1), BSR2018124. (doi: 10.1042/BSR20181246) (PMID:30563926) (PMCID:PMC6340945)

Zagnoni, M. and Woolhead, C. (2018) Droplet-based microfluidic platform for intracellular ion channel drug discovery. Impact, 2018(7), pp. 68-70.

Robinson, P. J. , Pringle, M. A. , Woolhead, C. A. and Bulleid, N. J. (2017) Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation. Journal of Biological Chemistry, 292(17), pp. 6978-6986. (doi: 10.1074/jbc.M117.780742) (PMID:28298446) (PMCID:PMC5409466)

Cabrita, L. D. et al. (2016) A structural ensemble of a ribosome–nascent chain complex during cotranslational protein folding. Nature Structural and Molecular Biology, 23(4), pp. 278-285. (doi: 10.1038/nsmb.3182) (PMID:26926436)

Robinson, P.J. and Woolhead, C.A. (2013) Post-translational membrane insertion of an endogenous YidC substrate. Biochimica et Biophysica Acta: Molecular Cell Research, 1833(12), pp. 2781-2788. (doi: 10.1016/j.bbamcr.2013.07.003) (PMID:23872420)

Robinson, P.J. , Findlay, J.E. and Woolhead, C.A. (2012) Compaction of a prokaryotic signal-anchor transmembrane domain begins within the ribosome tunnel and is stabilized by SRP during targeting. Journal of Molecular Biology, 423(4), pp. 600-612. (doi: 10.1016/j.jmb.2012.07.023) (PMID:22867705)

Peterson, J.H., Woolhead, C.A. and Bernstein, H.D. (2010) The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding. Molecular Microbiology, 78(1), pp. 203-217. (doi: 10.1111/j.1365-2958.2010.07325.x) (PMID:20804452) (PMCID:PMC2950912)

Woolhead, C.A. , Johnson, A.E. and Bernstein, H.D. (2006) Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. Molecular Cell, 22(5), pp. 587-598. (doi: 10.1016/j.molcel.2006.05.021)

Woolhead, C.A. , McCormick, P.J. and Johnson, A.E. (2004) Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell, 116(5), pp. 725-736. (doi: 10.1016/S0092-8674(04)00169-2)

Peterson, J.H., Woolhead, C.A. and Bernstein, H.D. (2003) Basic amino acids in a distinct subset of signal peptides promote interaction with the signal recognition particle. Journal of Biological Chemistry, 278(46), pp. 46155-46162. (doi: 10.1074/jbc.M309082200)

Rodger, A. et al. (2002) Flow oriented linear dichroism to probe protein orientation in membrane environments. Physical Chemistry Chemical Physics, 4, pp. 4051-4057. (doi: 10.1039/b205080n)

Tissier, C., Woolhead, C.A. and Robinson, C. (2002) Unique structural determinants in the signal peptides of 'spontaneously' inserting thylakoid membrane proteins. European Journal of Biochemistry, 269(13), pp. 3131-3141. (doi: 10.1046/j.1432-1033.2002.02943.x)

Mant, A., Woolhead, C.A. , Moore, M., Henry, R. and Robinson, C. (2001) Insertion of psak into the thylakoid membrane in a 'horseshoe' conformation occurs in the absence of signal recognition particle, nucleoside triphosphates, or functional albino3. Journal of Biological Chemistry, 276(39), pp. 36200-36206. (doi: 10.1074/jbc.M102914200)

Robinson, C., Thompson, S.J. and Woolhead, C.A. (2001) Multiple pathways used for the targeting of thylakoid proteins in chloroplasts. Traffic, 2(4), pp. 245-251. (doi: 10.1034/j.1600-0854.2001.1r010.x)

Woolhead, C.A. , Mant, A., Kim, S.J., Robinson, C. and Rodger, A. (2001) Conformation of a purified 'spontaneously' inserting thylakoid membrane protein precursor in aqueous solvent and detergent micelles. Journal of Biological Chemistry, 276(18), pp. 14607-14613. (doi: 10.1074/jbc.M009600200)

Woolhead, C.A. , Thompson, S.J., Moore, M., Tissier, C., Mant, A., Rodger, A., Henry, R. and Robinson, C. (2001) Distinct albino3-dependent and -independent pathways for thylakoid membrane protein insertion. Journal of Biological Chemistry, 276(44), pp. 40841-40846. (doi: 10.1074/jbc.M106523200)

This list was generated on Thu Apr 18 10:35:24 2024 BST.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Droplet-based Microfluidic Platform for Intracellular Ion Channel Drug Discovery
    Engineering and Physical Sciences Research Council
    2016 - 2019
     
  • Folding and insertion of a bacterial inner membrane protein
    Biotechnology and Biological Sciences Research Council
    2010 - 2013
     
  • Incorporation of fluorescently modified amino acids into proteins for structural studies
    The Royal Society
    2008 - 2009
     

Additional information

Invited International Presentations

  • 2006: Rehovot, Israel - Kimmelman Center for Biomolecular Structure and Assembly, Weizmann Institute
  • 2006: Maryland, USA - Institute for Physical Science and Technology University of Maryland, College Park, MD
  • 2005: San Francisco, USA - American Society for Cell Biology 'Protein Folding & Quality Control' Symposium
  • 2004: Hamburg,Germany - Spatio-Temporal Interactions of Cellular Signaling Molecules
  • 2001: Acquafredda di Maratea, Italy - European Science Foundation: Protein Targeting

Professional Learned Society

  • 2000 - present: Biochemical Society - Member

Research Fellowship

  • 2005 - 2007: NIH NIDDK Scientific Directors Fellowship

19 - 152 MVLS Staff Profiles Cheryl Woolhead158