Dr. Richard Goodwin
MALDI imaging mass spectrometry (IMS) on heat stabilized tissue to analyze peptides and small molecules
Senior scientist Dr Richard Goodwin is part of the newly formed group “Mass spectrometry Imaging and Profiling” within the in vivo DMPK at Astra Zeneca (UK). He is responsible for setting up an in-house MS Imaging analytical lab to support all Innovative Medicines Units (e.g. oncology, infection, immunity, respiratory and inflammation, cardiovascular and neuroscience research) across the company.Within the DMPK department, the focus is analysis of small molecule drugs and drug metabolites in plasma. But in addition to this, there is a great demand to determine tissue abundance and the distribution of small molecule drugs and drug metabolites using MALDI Imaging.
Richard obtained an undergraduate degree in genetics, and moved on to study fungal microbiology using Mass Spectrometry during his doctoral studies. During his first post doc position he focused on proteomic MS imaging. In 2006, he first started working with MALDI Imaging and was responsible to set up a MALDI Imaging facility at the University of Glasgow with the objective to implement and improve on proteomic tissue analysis. In 2011 he started a post doc position within Astra Zeneca (Sweden), where Richard continued to develop the MALDI Imaging technique but switched focus from large to small molecule analysis.
MALDI Imaging and the drug development process
MALDI Imaging has primarily only been implemented in the drug development process for the last four to five years but it has already become a widely utilized technique as it generates an improved understanding of the distribution of compounds in tissue samples. To date, MALDI Imaging is applied in the discovery phase, early compound development and toxicology studies.
Challenges with protein degradation
During Richard´s post doc period at Glasgow University, he encountered issues with immense sample variability in his proteome tissue analysis. The poor reproducibility limited his ability to generate meaningful results. Richard realized that the time from sample collection and snap freezing to analysis added a huge degree of variability. He saw substantially different peptide distributions due to this degradation, which increased with time before analysis. At a scientific conference in 2008, Richard first came in contact with Denator´s heat stabilization technology. He evaluated the technique which clearly limited degradation of proteins once samples were sectioned by cryomicrotome and analyzed by MALDI imaging. Shortly after the evaluation, he published a scientific paper covering the aspects of sample variation within MALDI Imaging and the importance of high quality sample preparation procedures to achieve high quality data.
Richard is somewhat surprised that sample preparation and the quality of the sample is often overlooked and skipped over as a formality by people working with MALDI Imaging. Richard continues “if you want to have truly reproducible and meaningful data generated the sample quality is as important as the sensitivity of the mass spectrometer”
In his first study, Richard encountered somewhat poor quality of the heat-stabilized tissue sections. Recently, Richard helped Denator in the development of guidelines on how to perform cryosectioning on heat-stabilized tissue in order to maintain the fine structure and the integrity in the tissue sample. One minor drawback with heat stabilization is that the overall tissue dimension is marginally squashed which slightly complicates things if you, for example, want to do calculation of tissue density. But Richard concludes “however, you cannot compromise on heat stabilization, it is a huge benefit being able to look at the compound and metabolite and its distribution in tissue. Heat stabilization gives us a whole new avenue being able to study the distribution of compound that we know would be affected by either degradation of proteins or suppression of ionization due to enzymatic activity in the tissue.”
Implementation of heat stabilization
Before implementing heat stabilization as a standard procedure in sample collection at a pharma company, extensive validation work is required to demonstrate its effectiveness. The priority for the group in the near future is to set up the lab and therefore they can’t prioritize such validation work. This may well change as Richard sees a great benefit of heat stabilization and believes it would be optimal to use the Stabilizor instrument in the animal facility for sample collection. Moreover he finds the instrument easy to use as “it´s just to plug and play”, it is rapid and enables generation of consistent MALDI Imaging data.
Publications from Dr Richard Goodwin utilizing the Stabilizor technology
Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation. Goodwin et al., Journal of Proteomics. Aug 2012. Vol. 75, issue 16, 4912-4920
Keywords: Peptides, MALDI MS imaging, rat tissues
Stopping the clock on proteomic degradation by heat-treatment at the point of tissue excision. Richard J. A. Goodwin et al. Proteomics, Volume 10, Issue 9, pages 1751-1761, No. 9 May 2010
Keywords: Mouse brain, MALDI-imaging, 2D-GE, mass spectrometry
Protein and peptides in pictures: imaging with MALDI mass spectrometry, RJ. Goodwin et al. Proteomics., 2008 Sep;8(18):3785-800
Keywords: Mammalian tissue, MALDI-imaging