2010 IR Workshop

Frank Martin

[Click here for the talk abstract]

Biography

Frank Martin is a Senior Lecturer at Lancaster University (UK) where he is also Director of the Centre for Biophotonics. Frank established his laboratory at Lancaster University in 2001 and his interests lie in the areas of stem cell biology and imaging (primarily gastro-intestinal tract and cornea), aetiology of cancer (primarily breast and prostate), role of cytochrome P450s (primarily CYP1B1), genetic toxicology and low-dose effects of environmental contaminants.

In this time he has received >£5million in research funding from Research councils (EPSRC, BBSRC), charities (NWCRF, Rosemere Cancer Foundation) and industry. He has several collaborations worldwide, including with groups at NIH (US), Institute of Cancer Research (UK), and DKFZ (Germany). He has published >100 original articles in leading peer-reviewed journals. Prior to his current role, Frank worked for 6 y at the Institute of Cancer Research (UK) as a Postdoctoral Fellow conducting research into the aetiology of breast/prostate cancer and genetic toxicology studies, primarily the development of the alkaline single cell-gel electrophoresis (comet) assay as a biomonitoring tool to ascertain single-strand breaks in individual cell genomes.

Frank completed his MSc at University of London (Experimental Pathology/Biochemical Toxicology, 1989) and his PhD at University College London (Studies into acetaminophen-induced mechanisms of hepatotoxicity, 1994).

Abstract

Biospectroscopy to characterise the stem cell lineage within complex tissue architectures
Dr Francis L Martin, Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK; f.martin@lancaster.ac.uk

The building blocks of a tissue’s architecture are multiple cell types that are at various points in lineages towards differentiation or their useful lifespan. Cell-specific functionality will determine chemical composition of bio-molecular structures. However, even similar cells with common functionality would be expected to differ in their chemical fingerprints. In general, tissues with a regenerative capacity (e.g., the GI tract) are believed to contain stem cells (SCs) that divide symmetrically or asymmetrically to give rise to transit-amplifying (TA) cells that are then committed to generating terminally-differentiated (TD) cells.[1]

Especially in human-derived tissues, application of conventional methodologies such as antibody-labelling of single epitopes has failed to result in convincing SC markers. In contrast, application of biospectroscopy methods generates an integrated chemical signature in the form of a spectrum; this can then be related to structure and function.[2] Given the number of data points within such a signature (typically 200 to 300) and the differing cell dynamics in a given tissue, large and complex datasets are generated.

Extracting the vital cell-specific discriminating variables can initially be approached using exploratory approaches such as principal component analysis and/or linear discriminant analysis.[3] There is already compelling evidence that such an approach can segregate putative SCs from TA cells from TD cells in different tissues.[4] Ultimately, this could allow one to identify the spectral profile considered normal; deviations from this would point to various pathological states.[5] In the future laboratory setting, biospectroscopy methods will shed novel microscopic insight into the function and role of the stem cell.

  1. Walsh MJ, Fellous TG, Hammiche A, Lin W-R, Fullwood NJ, Grude O, Bahrami F, Nicholson JM, Cotte M, Susini J, Pollock HM, Brittan M, Martin-Hirsch PL, Alison MR, Martin FL (2008) Fourier transform infrared microspectroscopy identifies symmetric PO2- modifications as a marker of the putative stem cell region of human intestinal crypts. Stem Cells 26: 108-118.
  2. Martin FL, Kelly JG, Llabjani V, Martin-Hirsch PL, Patel II, Trevisan J, Fullwood NJ, Walsh MJ (2010) Distinguishing cell types or populations based on the derivation and computational analyses of their infrared spectra. Nature Prot. In press.
  3. German MJ, Hammiche A, Ragavan N, Tobin MJ, Cooper LJ, Matanhelia SS, Hindley AC, Nicholson CM, Fullwood NJ, Pollock HM, Martin FL (2006) Infrared spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell. Biophys J 90: 3783-3795.
  4. Walsh MJ, Hammiche A, Fellous TG, Nicholson JM, Cotte M, Susini J, Fullwood NJ, Martin-Hirsch PL, Alison MR, Martin FL (2009) Tracking the cell hierarchy in the human intestine using biochemical signatures derived by mid-infrared microspectroscopy. Stem Cell Res 3: 15-27.
  5. Kelly JG, Nakamura T, Kinoshita S, Fullwood NJ, Martin FL (2010) Evidence for a stem-cell lineage in corneal squamous cell carcinoma using synchrotron-based Fourier-transform infrared microspectroscopy and multivariate analysis. Analyst (In press).