Dr Sarah Jones is a Lecturer in Pharmacology and a member of the Molecular Pharmacology Research Group. For the past 15 years, Sarah’s research has focussed on Cell Penetrating Peptides as a means to reach and modulate biological events within the cell. The ability of Cell Penetrating Peptides to target numerous and previously elusive intracellular candidate sites for therapeutic interventions could offer unparalleled opportunities for drug development and expand the repertoire of novel “druggable” targets.
With over 40 publications to date, numerous speaker invitations at International Symposia and co-editor of the book Bioactive Peptides, Sarah is now an established figure within the field of Cell Penetrating Peptides. Additionally, she has organized 3 International conferences including; a joint FEBS/Biochemical Society 4-day lecture course "Cell Penetrating Peptides" held at the Royal Society 2013, a Zing sponsored conference "Peptide Therapeutics 2012" and a Biochemical Society Focused Meeting "Cell Penetrating Peptides 2007.
2005 Doctor of Philosophy Design Synthesis and Evaluation of Receptor Mimetic Peptides as Signal Transduction Modulators
University of Wolverhampton, Molecular Pharmacology Research Group
2000 BSc (Hons) Biomedical Sciences, First Class
University of Wolverhampton
Institute of Biomedical Science, the Presidents Prize, 2000
The Physiological Society, Undergraduate Prize for Physiology, 2000
Patients’ Aid Association Prizes, 1997 and 1998, for outstanding performance in the field of undergraduate Biomedical Science
1995 Diploma in Psychiatric Nursing/Registered Mental Nurse
University of Birmingham and the Queen Elizabeth College of Nursing, Birmingham
2015 Fellow of the Higher Education Academy
2015 Post Graduate Certificate Academic Practice (PGCE)
The Molecular Pharmacology of Cell Penetrating Peptides
Cell Penetrating Peptide Technologies now provide a means of delivering previously impenetrable cargoes into the cell’s interior. Currently, Sarah’s endeavours encompass the design, synthesis and evaluation of cell penetrating peptides which target intracellular protein-protein interactions. Such investigations include identification of novel cryptic cell penetrating peptides within key signalling proteins and evaluation of their applicability as biological modulators (Bioportides) of apoptosis, tumour angiogenesis and Parkinson’s disease pathophysiology. The latter of which comprised a pilot study funded by the Michael J Fox Foundation, “Evaluation of LRRK2-derived Bioportides as Functional Protein Modulators and Potential Therapeutics”.
Very recently, Sarah’s research has extended to the utility of cell penetrating peptides as novel site-specific intracellular delivery vectors into mammalian sperm. With the ability to deliver bioactive cargoes into the sperm’s interior, such a development now provides the research community with valuable tools to investigate and modulate fundamental processes of sperm physiology and pathophysiology.
Thus, 4 main foci of work which are gaining significant impetus include;
Bioportides (bioactive cell penetrating peptides) and Reproductive Health
Identification and refinement of bioportides capable of penetrating human sperm cells to modulate the activities of intracellular proteins that control motility and fertilisation capacity
Development of an Innovative Human Mast cell-based Therapeutic Platform
The utilisation of inert CPPs to deliver bioactive cargoes into discrete compartments of human mast cells, and so enable their subsequent exocytosis by the physiological activation of regulated secretion
Stabilised Bioportides for Therapeutic Development
Evaluating the influence of chemical modifications on the biochemical and pharmacological properties of second-generation (proteolytically stable) bioportides, thus identifying candidates for therapeutic applications (Parkinson’s Disease and tumour angiogenesis).
The design, synthesis and evaluation of potent antimicrobial mastoparan analogues with limited secretory and cytotoxic bioactivities towards human cells. Initial screening has been carried out in collaboration with Community for Open Antimicrobial Drug Discovery, Institute for Molecular Biosciences, The University of Queensland and Welcome Trust
Strong international collaborative ventures lie at the heart of the molecular pharmacology group and have recently led to the development of a novel glioma-homing peptidyl drug delivery system and European Patent. entitled “chimeric constructs between glioma-homing peptide and cell-penetrating peptide”, this joint patent is with CePeP III AB, Stockholm, Sweden and the University of Tartu, Estonia.
Since 2006, Sarah has delivered oral presentations at the biennial European Peptide Symposiums and additional speaker invitations include;
Cell Penetrating Peptides in Paris, July 2015
Cell Penetrating Peptides, The Royal Society London, UK, 2013 Conference Organiser, Chair and Speaker
MedImmune (AstraZeneca), Cambridge UK, 2012, seminar entitled “Bioportides”, Invited Speaker
The Michael J. Fox Foundation for Parkinson’s Research, The Edmond J. Safra Philanthropic Foundation Conference Room, New York. LRRK2 Assessment, 2012, Invited Speaker
Peptide Therapeutics, Lanzarote, Spain, 2012 Conference Organiser, Chair and Speaker
Chemistry and Biology of Peptides, Oxford University, UK 2009, Invited Speaker
4th International Peptide Symposium in conjunction with 7th Australian Peptide Conference and 2nd Asia-Pacific International Peptide Symposium, Cairns, Australia, 2007, Invited Speaker
British Council of Slovenia, Café Scientifique, Llubjana, Slovenia, 2007, Invited Speaker
Sarah has also been a Distinguished Speaker at Marcus Evans Evolution and Discovery Summits, Monte Carlo, Monaco.
During June 2014, bioportide technology (Pantechnia Ltd- John Howl & Sarah Jones) was selected for the final of the Royal Society of Chemistry’s Emerging Technologies Competition.
Peer-elected member of the Scientific Committee of the European Peptide Society (2016-2020).
Peer-elected member of the Protein and Peptide Science Group of the Royal Society of Chemistry.
Jones. S., Uusna, J., Langel, Ü. & Howl, J. (2016) Intracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlates. Bioconjug. Chem. 27(1), 121-129
Morris, J., Jones, S., Howl, J., Lukanowska, M., Lefievre, L. & Publicover, S. (2015) Cell penetrating peptides, targeting the regulation of store-operated 1 channels, slow
decay of the progesterone-induced [Ca2+ ]i signal in human sperm. Molecular Human Reproduction. In press.
Howl, J. & Jones, S. (2015) Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells. J. Control. Release 202, 108-117.
Howl, J. & Jones, S. (2015) Insights into the molecular mechanisms of action of bioportides: a strategy to target protein-protein interaction. Expert Reviews in Molecular Medicine 17, e1 doi:10.1017/erm.2014.24.
Howl, J. & Jones, S. (2015) Protein Mimicry and the Design of Bioactive Cell Penetrating Peptides. Methods in Molecular Biology, 1324, 177-190
Lukanowska, M., Howl, J. & Jones, S. (2013) Bioportides: bioactive cell-penetrating peptides that modulate cellular dynamics. Biotechnology Journal 8, 918-930.
Mehta, A., Shervington, A., Howl, J., Jones, S., Shervington, L. (2013) Can RNAi-mediated hsp90 αknockdown in combination with 17-AAG be a therapy for glioma? FEBS Open Bio 3, 271-278. http://dx.doi.org/10.1016/j.fob.2013.06.002.
Jones, S., Lukanowska, M., Suhorutsenko,J., Oxenham, S., Barratt, C., Publicover, S., Copolovici, D.M., Langel,Ü. and Howl, J. (2013) Intracellular translocation and differential accumulation of cell penetrating peptides into bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility. Human Reproduction 28, 1874-1889
Eriste, E., Kurrikoff, K., Suhorutšenko, J., Oskolkov, N., Copolovici, Dana, Jones, S., Howl, J., Laakkonen, P. and Langel, U. (2012) Peptide-based glioma-targeted drug delivery vector gHoPe2. Biocongugate Chemistry 24, 305-313
Howl, J.,Matou-Nasri, S., West, D.S., Farquhar, M., Slaninová, J., Östenson, G.C., Zorko, M., Östlund, P., Kumar, S., Langel, Ü., McKeating, J. and Jones. S. (2012)Bioportide: An Emergent Concept of Bioactive Cell Penetrating Peptides. Cellular and Molecular Life Sciences 69, 2951-2966.
Jones, S. &Howl, J.(2012) Enantiomer-specific bioactivities of peptidomimetic analogues of mastoparan and mitoparan: characterization of inverso mastoparan as a highly efficient cell penetrating peptide. Biocongugate Chem. 23, 47-56
Jones, S., Holm, T., Mager, I., Langel, U. and Howl, J. (2010)Characterisation of Bioactive Cell Penetrating Peptides from Human Cytochrome c: Protein Mimicry and the Development of a Novel Apoptogenic Agent. Chemistry and Biology 17, 735-744
Jones, S. & Howl, J. (2010) Applications of cell penetrating peptides as signal transduction modulators for the selective induction of apoptosis. In: Cell Penetrating Peptides: Methods and Protocols, Methods in Molecular Biology, (Langel, U. ed). Humana Press, New York, USA.
Howl, J. & Jones, S. (2009) Transport molecules using reverse sequence HIV-Tat polypeptides: not just any old Tat? (WO200808225). Expert Opin. Ther. Pat. 19, 1329-1333.
Howl, J & Jones, S. (2009) Bioactive Peptides. Taylor & Francis/CRC Press. ISBN 9781420061147.
Jones, S. & Howl, J. (2009) Mastoparans. In: Bioactive Peptides (Howl, J. & Jones, S. eds). Taylor & Francis/CRC Press. ISBN 9781420061147
Jones, S., Martel, C., Belzacq-Casagrande, A.S., Brenner, C. & Howl, J. (2008) Mitoparan and target-selective chimeric analogues: membrane translocation and intracellular redistribution induces mitochondrial apoptosis. Biochim. Biophys. Acta. Molecular Cell Research. 1783, 849-863
Farquhar, M.J., Harris, H.J., Jones, S., Nielsen, S.U., Brimacombe, C.L., Molina, S., Toms, G.L., Maurel, P., Howl, J., van Ijzendoorn, S.V.D., Balfe, P., & McKeating, J.A. (2008) Protein Kinase A dependent step(s) in Hepatitis C virus entry and infectivity. Journal of Virology. 82, 8797-8811.
Howl, J. & Jones, S. (2008)Proteomimetic Cell Penetrating Peptides. Int. J. Pept. Res. Ther. 14, 359-366.
Howl, J., Nicholl, I.D. & Jones, S. (2007) The many futures for cell penetrating peptides: how soon is now? Biochem. Soc. Trans. 35, 767-769.
Jones, S. & Howl, J. (2006) Applications of cell-penetrating peptides as signal transduction modulators. In: Handbook of Cell Penetrating Peptides, 2nd edition (Langel, U. ed) CRC Press, Washington, D.C.USA.
Jones, S. & Howl, J. (2006) Biological applications of the receptor mimetic peptide mastoparan. Current Protein and Peptide Science 7, 501-508
Jones, S., Farquhar, M., Martin, A. & Howl, J. (2005) Intracellular translocation of the decapeptide carboxyl terminal of Gi3α induces the dual phosphorylation of p42/p44 MAP kinases. Biochim. Biophys. Acta. Molecular Cell Research 1745, 207-214.
Foreman, M.A, Gu, Y., Howl, J.D., Jones, S. & Publicover, S.J. (2005) Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells. J. Cell. Physiol. 204, 704-713.
Jones, S. & Howl, J. (2004) Charge delocalisation and the design of novel mastoparan (MP) analogues: Enhanced cytotoxicity and secretory efficacy of [Lys5,Lys8,Aib10]MP. Regul. Pept. 121, 121-128.
Jones, S. & Howl,J. (2004) Amphiphilic peptide engineering: Charge delocalisation and the design of novel mastoparan analogues. In: Peptides 2004 (Flegel, M., Fridkin, M., Gilon, C. & Slaninova, J. eds) Kenes International, Tel Aviv.
Howl, J., Jones, S. & Farquhar, M. (2003) Intracellular delivery of bioactive peptides to RBL-2H3 cells induces ß-hexoseaminidase secretion and phospholipase D activation. ChemBioChem 4, 1312-1316.
Jones, S. & Howl, J. (2003) Cannnabinoid receptor systems: Therapeutic targets for tumour intervention. Expert Opin. Ther. Targets 7, 749-758.
Brown, J., Reading, S.J., Jones, S., Fitchett, C.J., Howl, J., Martin, A., Longland, C.L., Michelangeli, F., Dubrova, Y.E., & Brown, C.A. (2000) Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83. Lab. Invest. 80, 37-45.