It's that time of year again... when 4 dynamic labs (Johnston, Evans, Elks and King) meet to discuss all things phagocytes! We had an excellent day this year, with a 2 hour (slightly muddy) walk followed by science talks from the newbies and final years and an extremely difficult team building activity involving Lego (thanks Jason!). Followed, of course, by a couple of beers and a nice meal. Fun times, thanks for a great day everyone!
Sharpening the blunted neutrophil response to antimicrobial resistant fungal infection
Life-threatening invasive fungal infection is a major health problem in the immunocompromised, and emerging drug resistance is a major threat to global health. Fungal pathogens, such as Candida, Cryptococcus and Aspergillus, are experts at immune evasion. Neutrophils - the most abundant white blood cell in humans - are vital in immunity to fungal infection, and optimising their function is a novel and powerful strategy to combat infection. The role of the neutrophils in fungal infection has been well studied in vitro but is difficult to translate to in vivo models of infection.
We have shown that if properly activated, neutrophils are very effective at controlling fungal infection, highlighting their potential as therapeutic targets. We are especially interested in low oxygen (hypoxia) signalling (via the transcription factor Hif-a). Infection sites are profoundly hypoxic and neutrophils have evolved to function in this environment. Targeting Hif-a therapeutically to activate neutrophils could be used against fungal infection, subverting antimicrobial resistance. You will use the transparent zebrafish embryo infected with Candida albicans and Cryptococcus neoformans to understand how hypoxia signalling might be targeted to treat fungal infection.
Using zebrafish models we already know that the two Hif-a variants, Hif-1a and Hif-2a, have opposing effects on neutrophil control of bacterial infection. In this project we aim to understand whether neutrophils can be molecularly ‘tuned’, by modulating Hif-1a and Hif-2a appropriately, to better kill invading fungi. Using cutting-edge molecular biology and fluorescence microscopy techniques you will address:
1. How Hif-a signalling is protective against fungal infection
2. How targeting different Hif-a variants can fine-tune neutrophil behaviour during fungal infection
This project synergises the expertise of a number of internationally leading groups at Sheffield Medical School, using techniques that are well-established in our groups that have so far produced exciting results and require an enthusiastic PhD student to take forwards. You will join a young and vibrant research lab (http://elkslab.weebly.com/) and you will be well trained in molecular biology and microscopy techniques, as well as writing and presenting your science. The research will take place in a newly refurbished bespoke zebrafish infection laboratory.
This is an exciting new project in collaboration with Alison Condliffe, Violaine See (Liverpool), and Simon Johnston labs.
See details below. Closing date is the 6th January 2020
Our new paper is out in Frontiers in Immunology, looking at the induction of macrophage Tnfa after hypoxia/Hif-1alpha stabilisation. Well done to Amy for all her hard work! You can find the paper here:
Well done to Hannah for getting her work on retention signalling published in Frontiers in Immunology! Thanks to all co-authors for all their hard work, especially Steve and his lab members!
We're very sad to lose Dr Hannah Isles, as she's finished her PhD and post-doctoral studies.
Thanks for all your hard work Hannah, it's been an absolute pleasure having you around!
The whole of the Elks lab (and Renshaw lab) will miss you, but we're super-excited for you and your big move across "The Pond" to a post-doc position in New York, and look forward to some excellent future science interactions!
Living in Sheffield can be a complete joy, with the Peak District right on the doorstep! We took advantage of the unusually summery February weather and had a little evening bouldering session.
We have a new review out on Teleost contributions to mycobacterial research. Well done to Dan Berreda's group in Alberta, Canada who coordinated this review! Here you can read about other fish models (like goldfish), that have made very important contributions to our understanding of immunity that are all too often overlooked by the zebrafish community.
We have a new paper out in The Journal of Immunology.
To read in full follow this link:
Congratulations to all the authors!
We have competitively funded PhD opportunities to start in October 2019. The adverts can be found here:
The deadlines are the 21st and 23rd January 2019
Welcome to Holly Anderson who is a placement student from Sheffield Hallam with us for a year!
We also say a sad adios to Abdi and Liv, thanks for all your hard work since last Autumn.
We had great fun holding the Zebrafish Infection UK meeting (https://www.zebrafishinfection.co.uk/photos) in Sheffield yesterday with the Johnston Lab. It was a fantastic meeting with some great science on show.
Especially well done to our very own Piotr, who won the poster prize!
We have two competitively funded PhD opportunities to start in October 2018. The adverts are here:
Elks Lab news
What's going on with us :-)