Imaging our immune system: From Cell to Seahorse

Once the capital of the Roman province of Britannia inferior after its establishment in 71AD, York has developed and evolved to become a city rife with architectural wonders and renowned tourist attractions. The city’s significant contribution to advances in all aspects of science, most recently in biology and information technology is notable. Since its founding as a ‘plate glass university’ in 1963, The University of York has adopted an outstanding reputation as a research institution, boasting an impressive ‘technology facility’ and research department focusing on a diverse spectrum of topics from ‘ecology and evolution’ to ‘infection and immunity’.

GFP-labelled image of the ‘Seahorse’ cell ©University of York; Image credit: Amy Sawtell

To celebrate the extraordinary achievements of York in science and innovation, the ‘Grand tour’ was created, an exhibit comprising sixty images and associated messages distributed throughout the city to both enthuse and educate residents and tourists alike. One particular exhibition which could be found on the Piccadilly Street provided an image of two fluorescently labelled immortalised cancer cells, exploited by the ‘Coles group’ to study how immune cells migrate and interaction during immune responses.

The human immune system is a vastly complex and highly organised system of cells that collectively functions to prevent disease. The efficient initiation of immune responses to bacteria and viruses requires rapid movement of and interactions between the different cells found in the immune system.

One focus of the research in the Coles laboratory, in the Centre for Immunology and Infection, is to elucidate mechanisms by which cells move and interact during the immune responses. One of the PhD students in the Coles group, Amy Sawtell who generated the image, is funded by ‘GlaxoSmithKline’ and the ‘Biotechnology and Biological Sciences Research Council’ (BBSRC) to analyse the role of cell migration during the initiation of an immune response to bacteria that cause pneumonia (Streptococci pneumoniae). One aim of her work is to identify the role of a lipid (fat molecule), sphingosine-1-phosphate (S1P), in controlling the entry and exit of immune cells from lymph nodes (those organs that swell on your neck during sickness). Recently a new drug, Fingolimod (Gilenya®), has been approved for the treatment of Multiple Scerlosis which works by blocking S1P receptor function, trapping the T cells (adaptive immune cells) in lymph nodes. This prevents neurodegeneration through stopping T cells from entering the brain and destroying the myelin sheath (fatty layer which insulates neuronal axons).

The ability to visualise and analyse cellular migration is essential in immunological research. This is achieved through either classical methods involving mechanical crushing of tissues, or more favourably, through ‘4D imaging’. Amy Sawtell explains the advantages of imaging in visualisation of cells:

“Classic techniques in immunology such as flow cytometry involve basically mashing up something to observe the cells that are there, but don’t tell us anything about how the cells move or how the cells interact as the tissue architecture is destroyed. However, when using imaging, we can actually see where the cells are moving and their interactions.”

The rather striking picture (below) is of an immortalised cancer cell that can be used to detect the S1P lipid through the expression of a ‘Green fluorescent protein’ (GFP) tagged S1P receptor. Upon ligand binding, the GFP-receptor-ligand complex is internalised, allowing direct visualisation of S1P activity or drugs that can inhibit its receptor function. Coincidently, the cancerous cell in this image resembles a Seahorse. These immortalised cancer cells allow the study of a novel type of drugs including Fingolimod on immune cell function. The ‘Seahorse’ cell is undergoing a process of programmed cell death, also known as ‘apoptosis’, which might explain its unusual cell morphology.

As explained by Dr. Mark Coles, who leads the projects within the Coles group, a diverse range of techniques are exploited in each study to provide the most comprehensive understanding of cellular behaviour in the immune system:

“As a lab as a whole, we try to do a range of different types of techniques. We do imaging, in-vitro models, and also do some in-silico simulations to understand what’s going on. Combining these three techniques allows us to answer different types of questions on cell behaviour.”

In York, a state-of-the art microscope system in the Technology Facility permits 4D imaging of cells. The discoveries made using imaging techniques will help facilitate the development of drugs to treat neglected tropical diseases and autoimmune diseases such as Multiple Sclerosis or diabetes. The applications of these discoveries in the prevention of disease through drug development simply accentuate the importance of imaging technologies in better understanding the human immune system.

“It (the GFP-labelled image of the cancer cell) is a beautiful image; it’s thought provoking to people. But what we wanted to get over is the idea that imaging is a very powerful technology for understanding biology and medicine.....It is also is a very powerful technology that drug companies use to develop new therapeutics.”

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