Randall Division of Cell and Molecular Biophysics

Randall Division of Cell and Molecular Biophysics

Dr Brian Stramer is a research scientist at the Randall Division of Cell and Molecular Biophysics at Kings College London. The Randall Division of Cell& Molecular Biophysics continues the tradition of biophysics at King's established by Sir John Randall, which produced the famous studies of the structure of DNA by Rosalind Franklin and Maurice Wilkins.

Research in 'the Randall' has a strong interdisciplinary flavor and the team collaborates extensively with the Asthma, Allergy and Lung Biology, Cancer Studies, Cardiovascular, and Developmental Neurobiology Divisions. Brian is part of the Cell Motility and Cytoskeleton group focused on dissecting the role and regulation of the cellular cytoskeleton in controlling cell morphology, adhesion, and migration.

Brian received his PhD in Cell, Molecular and Developmental Biology from Tufts University in Boston, and then worked for four years as a postdoctoral fellow at the US/UK Royal Society Research Fellow, working with Professor Paul Martin at the University of Bristol. Whilst he was there Brian began using Drosophila to dissect the molecular events surrounding tissue repair and inflammation with an eye towards extrapolating any knowledge gained from this model to higher organisms and ultimately humans.

Brian's recent research has been exploiting the fly's inflammatory response to address questions surrounding the basic mechanisms of cell motility. Cell migration is a widely researched and clinically relevant process that, with a greater understanding, may allow the control of a number of pathologies including cancer metastasis. However, cell motility has primarily been investigated using cell culture models, which involves watching cells move on artificial 2-dimensional substrates. While these in vitro assays have been useful, allowing for high-resolution analysis of cell movement, there will always be questions surrounding the physiological relevance of studying cell movement ex vivo on tissue culture plastic.

One of Brian's future goals is to extrapolate his in vitro cell migration knowledge to in vivo physiologically relevant scenarios using the Drosophila inflammation model.  During his post-doc studies Brian showed that Drosophila 'blood' cells (hemocytes) respond and migrate to sites of damage and infection much in the same way as our white blood cells do (Stramer et al., J. Cell Biol. 2005).  Pertinent to his current research interests in cell migration is that the hemocyte wound response is completely amenable to live imaging using standard widefield or confocal microscopy. This in vivo chemotaxis assay, along with the genetic tractability of flies, creates a powerful model system to dissect the genes regulating migration when cells are in their natural environment.

To expand the scope of this in vivo motility assay Brian has recently developed fluorescent fly lines that allow for the dynamic visualization of the migratory machinery in hemocytes i.e. actin and microtubules.  This allows for a deeper assessment of the mechanisms behind, and the genes regulating, motility in these cells.  Confocal microscopy allows for high-resolution analysis of actin and microtubule interactions in hemocytes. 

In collaboration with Professor Paul Martin, and the University of Bristol Wolfson BioImaging Facility, this team is beginning to dissect the dynamics of microfilament interactions as well.  Using their newly acquired Improvision Spinning Disk Confocal, the team can rapidly acquire 3-dimensional time-lapse images with minimal photobleaching or cell toxicity, which allows the capture of time-lapse movies showing cells in vivo at a spatial and temporal resolution approaching that which can be obtained from cells in vitro.

Brian says “Volocity is very user friendly, allowing us to rapidly compile a time-lapse series taken from a number of different microscope platforms.  We can then very easily capture snapshots for publication purposes or generate .mov files to show in seminars. Nothing wakes people up from a post-lunch seminar better than a good time-lapse movie."

 

Drosophila hemocytes expressing fluorescent probes for actin (green) and microtubules (purple) and imaged on a Leica SP5 confocal microscope.  This Z-stack was 3 dimensionally reconstructed using Volocity’s HR Opacity renderer and a Quicktime virtual reality movie generated.  In the merged image, white reveals the colocalization of the two cytoskeletal probes.