Events in The Medical School

Infection, Immunity and Cardiovascular Disease seminars

Thursday 6th February 2020

Title: "Through the looking glass, trypanosome infections in zebrafish: seeing is believing!"

Speaker: Dr. Maria Forlenza, Wageningen University, The Netherlands.

Venue: Lecture Theatre 3, F Floor Medical School.

Time: 12:30pm - 1:30pm

Abstract: Trypanosomes are important disease agents of humans, livestock and cold-blooded species, including fish. Motility is central to their adaptation to the host’s environments and pathogenesis. However, visualising the behaviour of trypanosomes resident in a live vertebrate host has remained unexplored. Furthermore, trypanosomes are well known for their evasion mechanisms and ability to manipulate the host’s response. In this study, we describe an infection model of zebrafish (Danio rerio) with Trypanosoma carassii, a species closely related to the mammalian trypanosome T. brucei ssp. By combining high spatio-temporal resolution microscopy with the transparency of live zebrafish, we describe for the first time in vivo, the swimming behaviour of trypanosomes in blood and tissues of a vertebrate host and reveal novel swimming behaviours, adaptation strategies and attachment mechanisms. Next, taking advantage of the availability of transgenic lines marking innate immune cells, we report on the differential response of macrophages and neutrophils to T. carassii infection in vivo. Interestingly, we observed that trypanosome infection triggers a marked macrophages activation leading to the formation of foamy macrophages and an exacerbated pro-inflammatory response. To our knowledge this is the first report describing the swimming behaviour of trypanosomes in vivo and the development of foamy macrophages during an extracellular trypanosome infection.

If you would like to meet with one of the speakers during their visit, please contact Victoria Palmer who will be able to assist.

Wednesday 1st April 2020

Speaker: Dr Pedro Moura Alves, Ludwig Institute for Cancer Research, University of Oxford.

Time: 12:30pm - 1:30pm

Venue: Lecture Theatre 3, F Floor Medical School.

Title: "Spying on bacterial communication: AhR sensing of bacterial quorum and infection dynamics.”

Abstract: The interaction between a bacterial pathogen and its host can be viewed as an “arms race” in which each participant continuously responds to the evolving strategies of the other partner. A mechanism allowing bacteria to rapidly adapt to such changing circumstances is provided by density-dependent cell-to-cell communication known as Quorum Sensing (QS).

QS involves a hierarchy of signaling molecules, which in pathogenic bacteria is associated with biofilm formation and virulence regulation. Notably, some QS molecules are detected by the host, and these can provoke specific immune responses. However, the receptors and their signaling pathways that the host uses to eavesdrop on bacteria remain poorly understood.

We hypothesized that if a host sensor can detect and differentiate between bacterial QS molecules and their expression patterns, it will allow hosts to customize their immune responses according to the stage and state of infection. We have previously discovered that the host aryl hydrocarbon receptor (AhR) directly recognizes bacterial pigmented virulence factors, such as Pseudomonas aeruginosa (P.aeruginosa) phenazines.

Currently, our results demonstrate that infected hosts show differential modulation of host AhR signaling over the course of P. aeruginosa infection in zebrafish, mice, and human cells. Further, modulation of AhR signaling depends on the relative abundances of several classes of P. aeruginosa QS molecules. In vitro and in vivo studies show that the AhR not only detects P. aeruginosa QS molecules in a qualitative way but also quantifies their relative abundances.

Quantitative assessment enables the host to sense bacterial community densities that may have distinct gene expression programs and infection dynamics, and thereby to regulate the scale and intensity of host defense mechanisms, which can range from induction of inflammatory mediators to immune cell recruitment and bacterial clearance. We propose that by spying on bacterial quorum, the AhR acts as a major sensor of infection dynamics, capable of orchestrating host defense according to the status quo of infection.

Neuroscience seminars

There are currently no upcoming seminars.

Oncology and Metabolism seminars

Friday 24 January 2020

Oncology & Metabolism Seminar Series Hosted by Oncology 

Title: "The role WSB-1 in hypoxic breast cancer: from metastatic potential to targeting DNA repair”

Speaker: Dr Isabel Pires, University of Hull

Venue: Lecture Theatre 3, F Floor Medical School.

Time: 1:00pm - 2:00pm

Abstract: Dr. Isabel Pires is a lecturer and group leader at the University of Hull. Isabel did her PhD at the University of Manchester/CRUK Manchester Institute with Professor Caroline Dive. She then moved to the University of Oxford for a postdoc in Professor Ester Hammond's group at the CRUK/MRC Institute for Radiation Oncology. There Isabel became interested in understanding how the tumour microenvironment, particularly tumour hypoxia, leads to alterations in cellular behaviour, such as increased genomic instability, resistance to therapy, and increased metastatic potential. Of particular interest was the therapeutic targeting of these altered pathways for overcoming the inherent radio-resistance of hypoxic regions. Isabel has been at the University of Hull for since late 2012, and her work continues to focus on characterising cellular signalling pathways associated to hypoxia and their exploitation for therapeutic benefit, with a particular emphasis in improving response to radiotherapy.

If you would like to meet with one of the speakers during their visit, please contact Gillian Griffiths - g.l.griffiths@sheffield.ac.uk - who will be able to assist.

Friday 7 February 2020

Oncology & Metabolism Seminar Series Hosted by the Mellanby Centre

Speaker: Professor Christine Le Maitre, Sheffield Hallam University

Title: Developing Disease Modifying Therapies for Intervertebral Disc Degeneration and Osteoarthritis

Venue: Lecture Theatre 2, F Floor, The Medical School, University of Sheffield

Time: 1:00pm - 2:00pm

Biography

I am an innovative scientist, committed to collaborative research, driven to maximise academic potential through creativity and vision. Following completion of a Wellcome Trust funded PhD studentship, investigating: the role of the inflammatory cytokine, interleukin-1 (IL-1) in intervertebral disc degeneration at Manchester University, I remained in this field to complete 5 years of postdoctoral research investigating the cellular basis of the pathogenesis of disc degeneration. In 2008, I moved to Sheffield Hallam University (SHU) as a Senior Lecturer and established my own research group in musculoskeletal diseases. In 2014, I was promoted to Reader and to Professor in 2017. I lead the Tissue Engineering and Biomechanics Research Group at SHU which is a cross disciplinary research group spanning across the Biomolecular Sciences Research Centre and the Materials and Engineering Research Institute at SHU. I am an internationally recognised cell biologist with expertise in a number of multidisciplinary fields. My main focus is investigating the cellular pathogenesis of intervertebral disc degeneration and its links to low back pain. These studies enable the development of innovative therapies, such as: smart biomaterials to support regeneration of intervertebral disc; together with other musculoskeletal tissues including: bone and cartilage. More recent research has expanded the portfolio of tissue types investigated for regenerative approaches and to develop 3D culture models to enable the reduction and replacement of animal models. Tissue types of interest in ongoing projects include: small intestine; liver; skin and bladder. I also have research interests in understanding the potential of natural products as anti-cancer therapies, particularly identifying the active agents and elucidating their mechanisms of action.

My research to date has led to 2 patents, 76 publications with ~5700 citations a current H index of 31 and i10 index of 54. I have been invited to present at >40 national and international meetings and am an elected committee member of various societies and chairperson for DISCs. I have been successful in obtaining ~ £16.6 million in research funding to date as PI or CoI and as a collaborator on a further £2.7 million and contributing to £5.8 million in doctoral training alliance funding. I am passionate about supporting the next generation of researchers and am a UKCGE recognized research supervisor, I have supervised 14 PhD students to completion and currently supervise 7 doctoral students. I am currently Head of Research Degrees for the College of Health, Wellbeing and Life Sciences at Sheffield Hallam University.

Abstract

Back pain and Osteoarthritis are the leading causes of morbidity worldwide, approximately 40% of back pain is associated with degeneration of the intervertebral discs in the spine. No current therapies target the pathogenesis of these important conditions and are purely symptomatic or end stage surgical approaches. Thus, the development of therapies which target the pathogenesis are urgently needed. My research group is particularly interested in improving the understanding of the pathogenesis of these related conditions and utilising this knowledge to develop novel therapies which can modify the disease process and ultimately bring about a cure. This presentation will discuss key features of pathogenesis including the influence of cellular senescence, cytokines, matrix degrading enzymes, nerve and blood vessel ingrowth and the influence of load will be discussed with considerations for therapy. The potential utilisation of gene therapy, stem cell therapies and biomaterial approaches for regeneration will be introduced.

If you would like to meet with one of the speakers during their visit, please contact Gillian Griffiths - g.l.griffiths@sheffield.ac.uk - who will be able to assist.

28 February 2020

Dr Simon Boulton, The Francis Crick Institute, London, Title: TBC, Lecture Theatre, Weston Park Hospital

Friday 20 March 2020

Dr Andrew Blackford, University of Oxford, Title: TBC, Lecture Theatre 3, F Floor, The Medical School, University of Sheffield

Internal seminar series

The department also holds internal seminars - for more information, see the full programme.