Defining the patterns of structural conformation, association, activation and signal transduction for the four members of the Human Epithelial Growth Factor Receptor family (HER1-4); determination of the conformation and the interactions leading to deregulated cell signalling. Deriving models of ligand-induced behaviour exploiting combined single molecule and ensemble FLIM analysis and systems predictions. Establishing how this is influenced by feed-back loops and internal and external perturbations, e.g. HER mutations (seen in human subjects), receptor tyrosine kinase (RTK) inhibitors (RTKIs) and function-blocking antibodies.
Single particle imaging. Super-resolution imaging - e.g. STORM and Fluorescence Lifetime Imaging with Photobleaching (FLImP). Cryo-STORM, SuperSIL technology, and cryo-CLEM.
PhD in Biophysics. University of Keele. Thesis title: The molecular structure and function of striated frog muscle: X-ray diffraction studies with synchrotron radiation.
Marisa joined the LSF in 2008. Her research is geared to understanding the intricate network signalling behaviour of cells in their physiological environments within tissues. The aim is describing the basic molecular ingredients, the signalling pathways and the supramolecular structural and spatio-temporal rules regulating signalling outcomes. Methods employed include multi-dimensional and multi-colour single molecule fluorescence imaging, single pair and ensemble FRET and polarisation in conjunction with the modelling of behaviour at atomic resolution within a mathematical framework.
Tel: +44(0)1235 567034
Prof. Stanley W. Botchway
Senior Scientific Staff & STFC BioMedical Network Lead
Visiting Professor, Faculty of Health and Life Sciences, Oxford Brookes University
Honory Senior Research Fellow in the School of Biological Sciences, University of Bristol
Development of advanced microscopy, cellular DNA damage and repair, ultrafast biophysics, time resolved linear and non-linear fluorescence spectroscopy, and application of lasers to biology and medicine.
Honorary Professorship Oxford Brookes University
MSc (University of Bristol, Advanced Analytical Chemistry)
PhD (University of Leicester, ‘Characteristics of DNA Damage by ultra-soft X-rays and Upon Photoionization’)
Research Fellowship, Harvard Medical School, USA
Membership of International Societies
Full Member, Royal Society of chemistry, UK
Full Member, Radiation Research Society, USA
Full Member, Association of Radiation Research, UK
Stan joined the LSF group within the CLF department in 1998 as the Laser Microscopy and Imaging Facility Manager and Biosciences Lead. His research has centred on the development and scientific application of lasers to biology and medicine. He has developed novel laser applications including an ultrafast laser microbeam for cellular DNA damage and repair studies, advanced imaging instrumentation and spectroscopy including Multiphoton Fluorescence Lifetime Imaging Microscopy (FLIM), the development of new probes for cellular imaging, studies on cancer protein interactions and a principal and co-investigator on several Research Council Grants as well as several patents.
For publications please see:
https://www.ncbi.nlm.nih.gov/pubmed/?term=botchway+s (link opens in a new window)
Tel: +44(0)1235 446260
Dr. Daniel Rolfe
Data analysis, simulation and visualisation methods, algorithm and software development, in particular for bioimaging in the field of single molecule microscopy. EGFR signalling processes, user-oriented software development, automated software pipelines, data management. Translation of methods from astronomy to bioimaging.
Scientific Programmer (2005-2006, CCP4, Protein Crystallography)
PDRA (2001-2004, University of Leicester, Theoretical Astrophysics)
PhD (2001, Open University, Astronomy, “Accretion Flow and
Precession Phenomena in Cataclysmic Variables”)
MPhys (1997, Oxon, Physics)
After research in astronomy and astrophysics, where he developed and applied advanced data analysis and simulation methods to understanding astrophysical accretion and stellar evolution, Dan joined STFC, first developing automated analysis pipelines, supporting and training users for the CCP4 protein crystallography analysis project (www.ccp4.ac.uk), before being tempted in 2006 into the fast-moving world of single molecule microscopy and its application to the understanding of cell membrane receptors for cancer research. Dan currently leads a small team, split between STFC and the University of Cambridge, within the group of Marisa Martin-Fernandez that develops and applies advanced data analysis techniques for single molecule imaging, often translating techniques from astronomy, and supporting users of the OCTOPUS facility to exploit them. He is also developing, with STFC eScientists, tools and techniques for improved data management and efficient usage of computing facilities.
Tel: +44(0)1235 446025
Dr. Chris Tynan
Investigating how signal transduction by the Epidermal Growth Factor Receptor family of tyrosine kinase receptors is regulated by their conformation, their interactions with each other and also with constituents of the cell membrane and cytoplasmic molecules. Studying the relationship between deregulation of these signals and disease (e.g. cancer) and elucidating the effects of therapeutic drugs targeted to these receptors at the molecular level. Single molecule tracking of membrane proteins, Forster Resonance Energy Transfer as a tool for measuring intermolecular distances and super-resolution microscopy of cell and tissue samples.
PhD, University of Liverpool. ‘A quantitative Förster resonance energy transfer method reveals functionally relevant structural variations in ErbB transmembrane receptors in cells’.
Chris has been a member of the LSF since 2008 and is currently a postdoctoral research assistant for the BBSRC LoLa grant, Supra-molecular rules in signalling networks: A single molecule comparative study in cells and tissues.
Tel: +44(0)1235 457089
Dr. Selene Roberts
Using FRET-FLIM, single molecule and super-resolution fluorescence microscopy techniques to observe the responses of the Epidermal Growth Factor (EGF) family of Receptors to stimuli; primarily interested in the conformations that the EGF Receptor adopts during signal mechanisms in cells. Studying changes in protein structure and receptor interactions that occur during aberrant signalling in cancerous cells and in cells expressing mutated receptors (naturally occurring and purposefully designed mutations). Perturbing cellular systems to identify the effects of therapeutically-relevant small molecule inhibitors and antibodies on signalling mechanisms.
PhD in Biochemistry - University of Leicester. Title: Signalling via Vascular Endothelial Growth Factor Receptor Complexes
BSc Medical Biochemistry – University of Birmingham
Selene joined STFC in 2005 and the LSF at the Rutherford Appleton Laboratory in 2008. Her research aims to combine many scientific tools to advance understanding within the area of cancer cell biology. In particular she questions the structure-function relationship of proteins in their natural environment by developing cell and molecular biology methods, protein biochemistry, fluorescent labelling of ligands and antibodies and multi-dimensional and multi-colour single molecule and confocal imaging. Selene is also the project manager of the grant entitled “Supra-molecular rules in signalling networks: A single molecule comparative study in cells and tissues”.
Tel: +44(0)1235 567144
Dr. Sarah Needham
How the Epidermal Growth Factor Receptor family of tyrosine kinase receptors is involved in signalling in normal and diseased cells (e.g. cancer). Investigating the conformational structure of each of the receptors, when they interact and when they interact with other receptors in the family. Studying their interaction with the cell membrane, cytoskeleton and downstream signalling molecules, and the effects of therapeutic drugs targeted to these receptors at the molecular level.
PhD in Biology - University of York. Title: Pleiotrophin and oligodendrocyte process extension and motility.
MSC Biomedical Sciences- University of Wolverhampton
Sarah has been with STFC since 2005 and joined the LSF in 2008. Sarah is currently a postdoctoral research assistant working on the BBSRC LoLa grant, Supra-molecular rules in signalling networks: A single molecule comparative study in cells and tissues. Is a member of the Biochemical Society.
Tel: +44(0)1235 457088
Dr. Michael Hirsch
Single molecule investigations of HER bio-system perturbations in living cells introduced via fluorescent tyrosine kinase inhibitors
University Diplom (Germany) in Mathematics. PhD in Theoretical Chemistry, University of Leipzig, Germany.
Michael joined the LSF in 2009. He is part of the data analysis team of the functional biology imaging. He is developing feature detection, tracking and super-resolution methods for single molecule microscopy, ensemble analysis algorithms and tools and interfaces for users.
He has also experience in gene expression data analysis and analysis of chemical potential energy surfaces
He is author and co-author on over 20 publications.
Tel: +44(0)1235 567145
Dr Andy Ward
CLF OCTOPUS Facility - Senior Scientist
Andy obtained his PhD at the University of Bristol studying polymer chemistry and dynamic light scattering. He has been at RAL since June 2000 applying laser microscopy techniques to scientific fields including colloid science, aerosol physics, the life sciences and the application of optical tweezers to wider STFC facility projects. His specific interests are in (i) aerosol chemistry and light scattering properties (ii) surfactant and emulsion behaviour (iii) Raman spectroscopy combined with optical trapping for biological applications, and (iv) combination of optical trapping with imaging techniques suc as confocal, FLIM and TIF microscopy. He is author and co-author on over 50 publications.
Tel: +44(0)1235 446751
Operations Scientist within the LSF
Benji joined the LSF in 2009. He provides operational support and development on the single molecule TIRF and confocal microscopes and has implemented new techniques such as Alternating Light Excitation (ALEX) and automated stage control for tweezer trapping.
He is also researching the use of Adaptive Optics to correct aberrations in thick biological samples, for use with PALM/STORM imaging.
MPhys, University of Southampton
Tel: +44(0)1235 446176
Jianguo started his research in computational physics, then in medical/medical image processing, analysis, registration, reconstruction, and visualization. He is also, interested in client server technologies, and system integration. He joined the LSF in April, 2015 and works on building data management and analysis system for the OCTOPUS users.
Data management and analysis, system architecture and implementation. Medical/Biological image segmentation, registration, feature extraction, and tracking.
He is also researching the use of Adaptive Optics to correct aberrations in thick biological samples, for use with PALM/STORM imaging.
PDRF then RS ( 2001-2015, EMAP, MRC Human Genetics Unit, Edinburgh )
PDRF (1998-2001, Queen's University of Belfast)
PhD in Computational Physics - Wuhan Institute of Mathematics and Physics,
The Chinese Academic of Sciences.
Tel: +44(0)1235 567888
Jorge Bernardino de la Serna
In general, I am interested in the molecular basis for cellular communication during immunologically relevant processes, focusing in lipid-protein spatio-temporal interactions, distribution and arrangements. For this purpose, I employ high advanced dynamic and static optical micro-/nano-scopy, and spectroscopy, combined with a detailed data analysis and quantification. In particular, I am aiming to understand the mechanisms of membrane sensing and remodelling in T-cells at the resting state and during T-cell activation.
Membrane sensing and remodelling
I am aiming at better understanding the manner plasma and intracellular membranes communicate with their micro/nano-environment; gaining knowledge on how they perceive stimuli and decode signals and how they encode their responses and trafficking mechanisms; and learning the way they harbour supramolecular assemblies and favour particular lipid-protein spatiotemporal arrangements.
Super-resolution (STED-based) method development.
I am interested in exploiting the benefit of scanning-based superresolution to obtain nanoscopic information on cellular dynamic events. I am currently applying point and scanning fluorescence correlation spectroscopy (FCS), fluorescence cross- correlation spectroscopy (FCCS), and image correlation spectroscopy (ICS). I am also developing ways to detect environmental dynamic nano-scale changes employing genetically encoded biosensors and fluorescence lifetime imaging microscopy (FLIM). I am also interested in developing single cell manipulation techniques to better control, sense and measure molecular events (forces, trafficking, and chemical sensing) during cell activation processes and cell-cell contacts.
Ph. D in Biochemistry. Master in Sc. degree in Biochemistry, and in Chemistry. Universidad Complutense de Madrid. Spain
Marie Curie Career Integration Grant. (2013-2017). “Nano -structural and -dynamic events in the T-cell activation
Tel: +44(0)1235 447726
Dr. Lin Wang
Super-resolution optical imaging, with a strong focus on PALM/STORM and its application in a wide range of biological studies.
Postdoctoral Research Associate, University of Sheffield. 05/2010-11/2015 Development of super-resolution single molecule localisation microscopy (PALM/STORM), wide-field and confocal laser scanning spectral microscopy, fluorescence life-time imaging microscopy, advanced total internal reflection fluorescence (TIRF) microscopy and other novel optical microscopy, to characterize the structure and function of biological photosynthetic membranes and light-harvesting protein complexes. Ph.D in Electrical and Electronic Engineering, University of Nottingham. 09/2006-9/2010 Development of structured illumination solid immersion fluorescence microscopy (SISIM), a wide-field microscopic technique to obtain sub-100nm lateral resolution by combining solid immersion lens technique and structured illumination microscopy.
Lin joined the CLF Octopus facility in September 2015 as a Super-resolution Microscopist. His role is to lead the user operation programme in the area of single molecule localization microscopy (PALM/STORM). He is responsible for working with facility users in planning of experimental programmes, data acquisition and data analysis, developing the STORM technique and instrumentation, liaising with the potential user community to achieve high quality facility access proposals.
Tel: +44(0)1235 445403
Dr. Laura Zanetti-Domingues
MSc in Biotechnologies, University of Milan
Laura joined the LSF in 2010 as a joint PhD student in Cancer Studies with King’s College London. She works under the supervision of Dr. Martin-Fernadez and is involved in the BBSRC LoLa grant. She is currently working at multicolour tracking of EGFR family receptors on the surface of live breast cancer cells.
Tel: +44(0)1235 567817
Dr. Alessia Candeo
Alessia completed her MSc in Physics Engineering and her PhD in Physics at Politecnico di Milano, Italy, in 2016 with the thesis “Calcium imaging by light sheet fluorescence microscopy”. Her main expertise is in laser physics and microscopy, with her research aiming to design new spectroscopy and imaging technologies for molecular biology. In this context, she focused her attention to functional studies of in vivo organisms, especially on Arabidopsis thaliana plants and the zebrafish brain.
Alessia joined LSF in July 2017. Her current role is to lead the user programme in the area of microscopy for life science, with her main expertise being light sheet fluorescence microscopy.
Tel: +44(0)1235 567732
Dr. Amy Moores
- PhD in Physics, University of Sheffield. Title: “Developing a Tip-Enhanced Fluorescence Microscope for Applications in Super-Resolution and Correlative Imaging”.
- MPhys in Physics with Medical Physics, University of Sheffield.
Amy joined the CLF in October 2017 as a post-doctoral research assistant. She works under the supervision of Dr. Lin Wang. Her research interests include correlative microscopy for biological applications, with a particular interest in super-resolution techniques. She is currently working on characterising the photophysics of fluorescent proteins under cryogenic conditions.
Tel: +44(0)1235 567047
- MSc in Radiation Biology at the University of Oxford. Awarded the Oxford Institute for Radiation Biology (OIRO) scholarship.
- BSc in Biomedical Science at Oxford Brookes University
Sarah joined us in January 2018 and is doing a 4-year PhD project with funding from BBSRC. She works under the supervision of Dr. Selene Roberts and her project will be to use super-resolution cryo-correlative light and electron microscopy (cryo-CLEM) to study the Epidermal Growth Factor Receptor (EGFR), studying changes in protein structure and receptor interactions that occur during aberrant signalling in cancerous cells. Part of her PhD will involve a placement at Linkam Scientific.
Tel: +44(0)1235 445941
Michele Guastamacchia (EngD student)
Bachelor Degree in Material Science and Master Degree in Science and Technology of Materials at University of Bari, Italy.
Michele joined the RAL in 2014, as a result of the collaboration between Heriot-Watt University in Edinburgh and the Rutherford Appleton Laboratory, as a Research Engineer for the Industrial Doctorate Centre in Optics and Photonics Technologies. Under the supervision of Dr. Stephen Webb and Dr. Paul Dalgarno, his research combines PALM/STORM microscopy with multifocal imaging, for 3D super-resolution imaging of extended samples.
Tel: +44(0)1235 447880
Abdullah Ahmed (PhD student)
Bachelor of Science degree (BSc) in biochemistry at the University of Birmingham, England.
mTOR signalling, cell signalling, fixed cell and live cell imaging using confocal microscopy, developing and using fluorescent technology to observe localisation and interactions of proteins in conjunction with FLIM, as well as determining structural protein information by X-ray crystallography.
Abdullah joined us towards the end of 2014 and is doing a 3 to 4-year project jointly supported by Evotec and STFC with full funding from BBSRC. He will develop fluorescent protein technology to investigate the activation and signalling pathways of mitogen induced proteins involved in signalling pathways and cell growth in particular, mTORC1 and mTORC2. The programme of work will use cell biology, immunohistochemistry and fluorescently tagging of proteins as well as a variety of imaging and optical techniques. He will be using the OCTOPUS cluster to investigate the conformation and interactions of individual molecules. A significant part of his research programme will involve the production of single crystals for X-ray crystallography at the Diamond Light Source at Harwell as well as the spectroscopic characterisation.
Tel: +44(0)1235 445574
Teodor Boyadzhiev (PhD Student)
Teodor joined RAL in 2014 as a PhD student from King's College London. His project is automated classification of intensity sequences, generated by fluorophores.
Machine Learning, Probabilistic Modelling, Evolutionary Algorithms
BSc Artificial Intelligence and Computer Science at The University of Edinburgh, Edinburgh, United Kingdom
Tel: +44(0)1235 567780
Sofia D'Abrantes (PhD Student)
Bachelor of Science degree with Honours in Biomedical Science at The University of Kent, England.
Cellular DNA damage and repair in relation to cancer, DNA binding proteins, live cell imaging, fluorescence technology, and fluorescence-lifetime imagining microscopy.
Sofia is a first-year Oxford Interdisciplinary Bioscience DTP (Doctoral Training Partnership) student. Using a range of microscopy techniques Sofia has been studying the kinetics and interactions of key DNA damage repair proteins. Using procedures such as molecular cloning, CRISPR/Cas9 technology, immunohistochemistry, fluorescent tagging of proteins and western blotting, Sofia hopes to further investigate the dynamics of these proteins in live cells.
Tel: +44(0)1235 567783