Peter J S Smith
- Primary position:
- Director, Institute for Life Sciences (IfLS)
- Other positions:
- Professor of Life Sciences, Faculty of Natural and Environmental Sciences, Principal Investigator (Biophysics & Cell Biology)
2011-present Director, Institute for Life Sciences (IfLS), University of Southampton, England
2011-present Professor of Life Sciences, Faculty of Natural and Environmental Sciences, Univ. of Southampton.
2008-2011 Director, Cellular Dynamics Program, Marine Biological Laboratory (MBL), USA
2008-present Visiting Professor, Dept. of Engineering, University of Edinburgh, Scotland.
2008-2011 Executive Committee, Clinical Science Translational Initiative Brown Univ., USA
2008-2011 Adjunct Professor of Engineering (Research), Brown University, RI
2007-2011 Member, Institute for Molecular & Nanoscale Innovation, Division of Engineering, Brown Univ.
2007-present Honorary Professor, School of Electronic Engineering, University of Wales
2002-2008 Director, Molecular Physiology Program, MBL
1999-2011 Senior Scientist, MBL
1996-2010 Director and Principal Investigator, NIH BioCurrents Research Center, MBL
1994-1996 Director and PI, NIH National Vibrating Probe Facility, MBL
1992-1993 Co-Director, NIH Nat’l Vibrating Probe Facility, MBL (With L. F. Jaffe)
1992-1999 Associate Scientist, MBL
1990-1991 Senior Scientific Officer and Lab. Leader, AFRC Laboratory of Molecular Signalling, Dept. of Zoology, University of Cambridge and the Babraham Research Institute, UK
1987-1990 Higher Scientific Officer, AFRC Unit of Insect Neurophysiology and Pharmacology, Dept. of Zoology, University of Cambridge, UK. Glial cell biology
1986-1991 Fellow and Director of Studies in Natural Sciences, Sidney Sussex College, Cambridge, UK
1985-1987 Leverhulme Research Fellow, University of Cambridge, Dept. of Zoology, Cambridge. Glial cell biology: mechanisms of brain repair
1982-1984 Research Associate, University of Cambridge, Dept. of Zoology, Cambridge, UK. Insect glial and neuronal physiology and anatomy. (With J. E. Treherne)
1979-1982 Research Associate, University of Manchester, UK. Neurobiology. (With D.M.Guthrie)
The University of Southampton's electronic library (e-prints)
My interests lie in monitoring cells, in health and disease, by targeting the dynamics of living systems. In particular, I’ve been interested in following cell activity non-invasively by sampling chemical profiles in the unstirred layers surrounding single cells and tissues. The unstirred layer is surprisingly deep. In still culture medium estimates range up to 300m and even in flowing medium this layer can be 10s of microns in depth. There is ample volume for establishing chemical gradients in the boundary layers that result from cell activity and ample space for deploying electrochemical sensors of micron diameters within these layers. Chemical signals are quite strong, particularly when backgrounds and/or competing chemicals are low in activity. However, instabilities in the electrode and the recording circuit frequently prevent extraction of useful data. Here a modulation technique, termed self-referencing, comes into play. With this technique an electrochemical microelectrode records chemically dependent signals at two positions and a differential is calculated. This results in a 1000 fold improvement in resolution over the same electrode in a static configuration. Both potentiometric and amperometric sensors can be used, delivering high spatial and temporal fidelity. (See Smith et al. 2010 Bioessays 32 514-523).
Current research aims to explore opportunities unique to Southampton.
- Non-invasive sensing of cell dynamics
Single cells are addressed using novel methods in cell manipulation, light and electrochemistry.
- Manipulating cell metabolism
Building on recent studies with hippocampal neurons (see below) further work targets the metabolism of cancer cells.
- Providing resources for cell observation
Transferred technology opens access to researchers for self-referencing measurements built around a spinning disc confocal and electrophysiology platform.
Case studies illustrate the strength of the microsensor approach and two examples are given below. References covering ion transport, as well as oxygen, nitric oxide, glucose, lactate and others, can be found in: Smith et al. (2007) Principles, Development and Applications of Self-Referencing Electrochemical Microelectrodes to the Determination of Fluxes at Cell Membranes. In: Methods and New Frontiers in Neuroscience. Ed. Adrian C. Michael. CRC Press. Chapter 18
Case Study 1: Oxygen consumption from identified neurons in culture
In collaboration with investigators at Yale and Johns Hopkins, micro-oxygen electrodes were used to monitor metabolism in identified transfected hippocampal neurons. Monitoring single neurons, expressing Bcl-xL, showed novel metabolic regulation through the interaction of the anti-apoptotic protein Bcl-xL with the mitochondrial F1FO ATP synthase. Healthy neurons use Bcl-xL to produce a different kind of metabolic efficiency. The changes in metabolism produced by Bcl-xL may also enhance resistance to pathological stressors including hypoxia and substrate deprivation. Further, Bcl-xL may also maintain cytosolic ATP levels in the face of the increased energy demand during synaptic development, and long- or short-term changes in synaptic plasticity. These data indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-xL-expressing neurons. (Alavian, K. et al. 2011. Nat Cell Biol 13(10), 1224-1233. See also; Li, H. et al. 2008 Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc. Natl. Acad. Sci. USA 105, 2169-2174).
Case Study 2: Proton pumping in the epididymis
With collaborators at Harvard and Massachusetts General Hospital we focussed on the mechanisms behind the acidification of fluid in the epididymis. This was an in vitro tissue study where a potentiometric hydrogen selective microelectrode was scanned across the surface of an excised and opened section from the epididymis. Our studies rapidly identified a role for the vacuolar-type proton ATPase (Breton et al. 1996 Nat . Med. 2, 470-472). The ion selective microelectrode then became a workhorse approach to testing the functional impact of various treatments, delivering an ever more refined understanding of the cellular mechanisms underlying pump function and trafficking. The study recently culminated in demonstrating that transepithelial projections from basal cells function as luminal sensors in pseudostratified epithelia, modulating epithelial function by a mechanism involving crosstalk with other epithelial cells (Shum et al. 2008 Cell 135, 1108-1117).
Affiliate research group: Imaging in the Nanodomain
Primary research group: Institute for Life Sciences (IfLS)
The principal aim of this project is to demonstrate sensing in the extracellular/intercellular space using functionalized quantum dots. Spatial and temporal information on intercellular concentrations will allow us to study how analyte concentrations in the EICS are linked to physiological status.
- 2013-2015 Principal Investigator on BBSRC Sparking Impact Competition entitled: Excellence with Impact. £26,539 (Direct)
- 2013-2014 Co-Principal Investigator on Southampton Imaging: 3D Imaging at millimetre to nanometre scales for regenerative medicine using multiple complimentary modalities. With Richard Oreffo (PI) Medicine, Anton Page ( Medicine), Peter Lackie ( Medicine), Ian Sinclair ( Engineering). MRC Award £1.171M - Capital Equipment for Regenerative Medicine.
- 2013 - 2014 Principal Investigator on University of Southampton Enterprise Fund, Nanoscope: Translation to biomedical applications and markets. Co-Is. Dr John Chad (FNES) Dr Tracey Newman (F0M). Advisor N. Zheludev (FPAS). £89,000
- 2013 - 2014 Co-Principal Investigator on EPSRC Laser-printable point-of-care sensors for low-cost medical diagnosis and disease monitoring. Principal Investigator, Prof. Robert Eason, Optoelectronics Research Centre, Co-Investigators Dr Spiros Garbis Cancer Sciences, Dr Saul Faust Medicine, Researcher-Co-Investigator Dr Collin Lawrence. £232,528 (FEC), £186,022 (EPSRC)
- 2013 - present Visiting Fellow, Marine Biological Association, Plymouth, UK
- 2012-present Co-supervisor with Ali Tavassoli of PhD student Ishna Mistry, Dept of Chemistry, University of Southampton. The project title is "Tolerating Hypoxia in Rapidly Growing Cells: Parallels between cancer and development"
- 2012-present Chair, Management Group, Wessex Life Science Alliance
- 2012-present Member, Joint Research Strategy Board, University of Southampton and University Hospital Southampton
- 2012-present Member, Health and Pharma, University Industrial Sector Team, University of Southampton
- 2012-present Board member, Zepler Institute, University of Southampton
- 2012-present Member, Faculty Health and Safety review group
- 2012-present Chair, Life Sciences Building Operations Group
- 2011-2014 Co-Principal Investigator on Australian Research Council Discovery Project (DP120104035): Charting Intercellular Space, M. H. Todd, P. J. Rutledge and P. J. Smith ($348K) Univ. of Sydney, Aust
- 2011-present Director, Institute for Life Sciences (IfLS), University of Southampton, England
- 2011-present Professor of Life Sciences, Faculty of Natural and Environmental Sciences, Univ. of Southampton
- 2011-present Appointed Trustee, Southampton University representative, Board, Wessex Medical Research
- 2011-present Adjunct Senior Scientist, Cellular Dynamics Program, Marine Biological Laboratory, Woods Hole, MA, USA
- 2011-present Representative, University of Southampton, Euro-Bioimaging Project
- 2011-present Member, Faculty of Physical and Applied Sciences Faculty Research Committee
- 2011-present Member, Faculty of Medicine Research Management Committee
- 2011-present Member, Centre for Biological Sciences Research Management Committee
- 2008-present Visiting Professor, Dept. of Engineering, University of Edinburgh, Scotland
- 2008-present Advisory Committee, Rockefeller Neuroscience Institute, West Virginia
- 1999-present Consultant, CIR Biomedical Technology and Engineering, Falmouth, USA