UKRI-BBSRC Grant Awarded to Samantha Pitt – High-resolution structure, function and anti-viral inhibition of the SARS-CoV-2 E protein ion channel

Dr Samantha Pitt and partners from University of Dundee (Prof Ulrich Zachariae) and Trinity College Dublin (Prof Martin Caffrey), have recently been awarded a UKRI-BBSRC grant to address problems related to COVID-19. Employing an interdisciplinary approach, the team will use structure-based drug design to accelerate the discovery of drugs to target SARS-CoV2 by enabling focused, rational approaches to design and repurposing. The project aims to i) solve high-resolution crystal-structures of CoV2E (ii) apply computational electrophysiology and in silico screens including cheminformatics/machine learning approaches to identify CoV2E inhibitors from libraries of commercially available and repurposing drugs, and (iii) perform lead validation and further development of inhibitors by electrophysiology and crystallography.

 

 

Dr Samantha Pitt becomes a commitee member of the Scottish Cardiovascular Forum

Dr Samantha Pitt has been invited to become a committee member of the Scottish Cardiovascular Forum to represent the University of St Andrews. The Scottish Cardiovascular Forum was launched in October 1997, with the aim of fostering integration, encouraging collaboration and assisting in the dissemination of information among basic science and clinical cardiovascular researchers in Scotland and further afield. https://www.scf.strath.ac.uk/index.php

Our paper in Nature Photonics is now available – Monitoring contractility in cardiac tissue with cellular resolution using biointergrated microlasers

Our latest collaborative work on microlasers as versatile contractility sensors in the heart is out.

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers” by Marcel Schubert, Lewis Woolfson, Isla R M Barnard, Amy M Dorward, Becky Casement, Andrew Morton, Gavin B Robertson, Paul L Appleton, Gareth B Miles, Carl S Tucker, Samantha J Pitt and Malte C Gather is published in Nature Photonics and available online.

In this work we show that implanted microlasers can scan heart tissue from inside cells.  Tiny lasers were placed inside the heart where they acted as microscopic probes. With every beat of the heart, the colour of light that these lasers emit changed by a small but clearly detectable amount, thus precisely encoding the contractions of the heart cells over time.

Although the research is still in its early days, the present study proves that lasers can resolve fast dynamic processes inside individual live cells and whole hearts.

Our University press release can be found here https://news.st-andrews.ac.uk/archive/feel-the-beat-implanted-microlasers-scan-heart-from-inside/

Our paper in Nature Communications is now available – Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets

Here we detail a new technique to trick bacteria into revealing hundreds of holes in their cell walls, opening the door for drugs that destroy bacterial cells. This interdisciplinary work shows for first time that MscL channels are kept closed by membrane lipids – specifically lipid chains- which are located within nano-pockets highly sensitive to tension, pressure and force. When access of these lipids is disrupted by molecular nano-guards engineered at the entrance of the nano-pockets, the channel mechanically responds and opens its pore. Targeting these pores may pave the way for new drugs that can destroy bacterial cells and could make current antibiotics more effective or allow for the development of antibiotic-free drugs that can use these openings.

Here is a link to our paper https://www.nature.com/articles/s41467-019-12591-x

International Society for Zinc Biology 2019 Meeting & Kyoto Lab Visit

3rd year BHF-funded PhD student Amy Dorward (Pitt lab) and Dr Gavin Robertson (PDRA; Pitt lab) visited Prof Hiroshi Takeshima’s lab at the Graduate School of Pharmaceutical Science, Kyoto University, Japan between 9th August – 14th September 2019. During this time both Amy and Gavin carried out some exciting new experiments, which will contribute to an upcoming publication.

Whilst in Kyoto, Amy, Gavin and Dr Samantha Pitt attended the International Society for Zinc Biology (ISZB) 2019 conference. They would like to thank the organisers for an excellent meeting. Samantha gave an invited talk entitled “Intracellular Calcium and Zinc Dynamics are Intrinsically Coupled”. Amy and Gavin both presented posters. Gavin was awarded a Metallomics poster prize.

Amy was awarded travel grants by Russell Trust, Biochemical Society, British Society for Cell Biology (BSCB) and the School of Medicine. Gavin obtained funding from BSCB and the Physiological Society.

   

Graduation Day for our BHF-Funded PhD Students

The Pitt and Stewart labs would like to say a big congratulations to Dr Gavin Robertson and Dr Amelie Sobczak on their graduation, and would also like to say a big thank you to the BHF for funding these students. #Ever to Excel

Samantha Pitt has been elected as a board member of the International Society for Zinc Biology

Dr Samantha Pitt has been elected as a board member of the International Society for Zinc Biology (http://iszb.org/). She will serve the Society for 2 years. She is very excited to contribute towards the future direction of the Society and will work to raise  the  awareness  of  the scientific  community  regarding  the  importance  of  zinc  in  health  and  disease.

 

Zinc-net meeting – 18th January 2019. Anglia Ruskin University, Cambridge, UK

The Metal Ions in Medicine team  attended the 2019 Zinc-net meeting in Cambridge, UK. This International meeting focused on investigating the role of zinc in biological systems. Dr Samantha Pitt gave the opening plenary lecture. The title of her talk was “Altered Zn2+ homeostasis in Niemann-Pick C1 disease results in impaired NAADP-mediated lysosomal Ca2+-dynamics”. Dr Alan Stewart gave a talk titled “Influence of free fatty acids on plasma zinc handling by albumin: Impact on coagulation in type II diabetes”. Gavin Robertson (BHF funded PhD student in the Pitt lab) presented a poster titled “Mitsugumin 23: a cardiac sarcoplasmic reticulum Ca2+ leak channel that displays Zn2+ permeability”.

The team would like to thank Dr Nick Pugh (Anglia Ruskin University) for organising this meeting.

Dundee Science Festival 2018

Amy Dorward (Pitt Research group) took part in the Dundee Science festival 7th October 2018. She volunteered at the British Heart Foundation’s “Air Street”. The exhibit focussed on the silent harmful effects air pollution has on the cardiovascular system. Visitors walked ‘outside’ along “BHF Air Street” – where posters outlined the main links of pollution and cardiovascular disease – before coming ‘inside’ to the “BHF sitting room” – where they learned more about the research being carried out by the BHF in their local area. Visitors were also given the opportunity to look at diseased and healthy heart cell cells under the microscope, measure their own heart rates and learn about how the heart works through a variety of activities. Amy really enjoyed volunteering at the festival and she is grateful to have had the opportunity to talk about some of the cardiovascular research being carried out in University of St Andrews.