The Schachter Award in action

Twice a year the British Pharmacological Society awards the Schachter Award to a postgraduate research student. The award provides up to £1,850 to support them to visit another laboratory to learn a new technique that cannot be conducted at their home institute. The award was established in 2002 by a generous donation to the Society from Mrs Ruth Schachter in memory of her late husband, Dr Melville Schachter.

Here, the two winners from 2016, Simon Cleary and Joanna Clarke, report on their Schachter Award visits and reflect on what they gained from their experiences.

Simon Cleary

Receiving the Schachter Award enabled me to visit the laboratory of Professor Mark Looney at the University of California, San Francisco (UCSF), USA. During this placement, from late October to the middle of December in 2016, I was able to learn intravital microscopy techniques for imaging cellular events in the living lung, and develop a new method to measure platelet adhesion in the context of lung inflammation.

My PhD project has been to develop methods to describe and measure the poorly understood phenomenon of recruitment of platelets to inflamed lungs, which may be important for driving inflammatory responses. Platelets are of interest to pharmacologists working to identify new targets for drugs to treat inflammatory lung diseases, and the research groups of my supervisors at King’s College London, Simon Pitchford and Clive Page, and Mark Looney’s group at UCSF, are trying to identify how platelets contribute to inflammatory responses in lungs to guide development of future therapeutic interventions.

Due to the small size of platelets and the position of the lungs inside the ribcage, directly visualising platelets in lungs requires slices of lungs that until now has necessitated killing a laboratory animal, or accessing autopsy or invasive biopsy samples from human donors. At UCSF, mice have been bred to have green fluorescent protein (GFP) expressed in their platelets.2 A small vacuum window, which sits between the ribs in order to immobilise the surface of the lung to a coverslip, is inserted into anaesthetised mice and with the use of a specialised multiphoton microscope (which can focus deeper into tissue than other regular microscopes) the GFP platelets can be observed moving through the bloodstream in the lung.

With direction from Mark Looney and working with postdoctoral fellows Emma Lefrançais and Beñat Mallavia, I captured multiphoton microscopy videos of platelets passing through healthy and inflamed mouse lungs, and developed a new method for analysing the resultant videos to determine the number of platelets that were adhesive to the lung as opposed to moving through the lungs in the blood.

This method has great potential for use as an in vivo pharmacological assay, and I am excited to use it again to help identify new targets and drug interventions for conditions such as inflammatory lung diseases and pulmonary thrombosis.

Thanks to the added interest in my work resulting from this opportunity, I have been invited to present this work at my first oral communication at an international conference at the International Society on Thrombosis and Haemostasis Congress in Berlin in July (come and say hi if you are going!). I am currently preparing a manuscript from my PhD thesis incorporating my work at UCSF and further investigations into the mechanisms of inflammatory platelet recruitment for submission as a journal article.

My visit to UCSF would not have been possible without the generosity of the Society and the Schachter family, and I am very grateful to both for this experience which has allowed me to grow as a scientist, to make new friendships, and has helped our laboratory to establish a new international collaboration.

Joanne Clarke

With the funding I received from the Schachter Award I was able to carry out work in Switzerland at the Novartis headquarters in Basel and the University of Zürich.

My PhD research concerns the evaluation of novel druginduced liver injury (DILI) biomarkers – molecules that can be measured to give an indication of liver status following a possible toxic event, highlighting any potential damage and thus enabling subsequent patient stratification.

At Novartis I was able to learn histological staining techniques (in situ hybridisation and immunohistochemistry) to detect several biomarkers within human liver tissue from healthy individuals as well as sections taken from patients following a liver transplant due to paracetamol overdose. These techniques are not currently available in my department at the University of Liverpool, so the opportunity to learn them was a really valuable outcome from this placement – and exactly the sort of opportunity the Schachter Award is designed to offer.

Following my three weeks at Novartis I moved on to the University of Zürich, where I was able to learn how to use and apply an innovative computer software that enabled the quantification of biomarker expression – allowing us to put numbers to our findings and make a closer assessment of the patterns we had detected.

There is a need for new biomarkers of DILI to complement current methods and improve our safety assessment of both new and existing medicines. The work I was able to carry out in Switzerland could facilitate a more comprehensive understanding of the underlying molecular events within otherwise inaccessible tissue, allowing us to piece together the evidence to better interpret and utilise biomarkers released from the liver. Ultimately, incorporation of these novel biomarkers to current methods can potentially make it easier to identify patients that need more intervention, while simultaneously reducing the number of patients that are being unnecessarily treated under current regimens (reducing the use of harmful and costly treatments and freeing up hospital beds in the process).

Learning and performing these techniques has not only improved my experimental knowledge and enabled me to attain valuable and novel data, but additionally these placements have given me a very useful insight into alternative research settings. At Novartis I was able to gain insight into the pharmaceutical industry, and my time at the University of Zürich gave me a flavour of how things are done in another academic department and indeed another country.

Both experiences gave me the opportunity to develop new professional connections, and the chance to work independently and abroad has definitely boosted my self-confidence.

I am really grateful to have had this opportunity. I thoroughly enjoyed my time in Switzerland; it was an incredibly productive trip that would not have been possible without the Society’s Schachter Award. I would like to acknowledge collaborators at the University of Edinburgh, UK as well as Aintree Hospital and the Transplant Unit, Edinburgh for provision of the samples involved in this project.

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