Events in The Medical School

Infection, Immunity and Cardiovascular Disease seminars

Wednesday 15th June 2022 at 2pm (GMT)

Speaker - Professor John Rawls, Duke University, USA.

Title - 'Using zebrafish to explore the integrative physiology of host-microbe interactions in the intestine'

Venue - Theatre 4, Arts Tower.

Apologies for any inconvenience this venue change will cause. This is due to estates work being undertaken at the Medical School which will affect the use of the lecture theatres on B Floor.

Abstract - Dr. Rawls has focused his scientific career on understanding how host-microbe interactions in the intestine contribute to health and disease. His lab uses gnotobiotic, in vivo imaging, genetic, and functional genomic approaches to determine how microbiota interact with vertebrate hosts to regulate physiologic processes. He pioneered the use of germ-free and gnotobiotic zebrafish to investigate the roles of microbiomes in vertebrate biology, and now uses complementary zebrafish and mice to investigate conserved bacterial signals and responsive host pathways that regulate host nutrition, immunity, and gene expression. He also recently expanded his lab’s studies to humans to define microbial species and metabolites that are associated with and potentially contribute to pediatric obesity and associated comorbidities.

Wednesday 6th July 2022 at 2pm (GMT) (Date has been changed from 16th March, please accept our apologies for any inconvenience this may cause)

Speaker - Dr Pedro Moura Alves, University of Oxford.

Title - 'AhR sensing bacterial quorum during infection'

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 13th May 2022 at 1pm (BST)

Internal Seminar Series

Friday 20th May at 1.00pm (BST)

Speaker: Professor Martina Rauner, TU Dresden.

Title: ‘Molecular Mechanisms of Diabetic Bone Disease'

Abstract: Martina Rauner studied biotechnology at the University of Applied Sciences in Vienna, Austria from 2002-2006. After completing her doctorate at the Department of Pathophysiology at the Medical University of Vienna in 2008, she received the ECTS/AMGEN bone research fellowship and joined the group of Professor Lorenz Hofbauer in Dresden, Germany to study mechanisms of glucocorticoid-induced osteoporosis. In 2011, Martina became Group leader for Osteoimmunology and expanded her research area to chronic inflammatory diseases and Wnt signaling. Due to her comprehensive knowledge on bone biology, its interactions with other organ systems, and her leadership skills, she was promoted to the Scientific Director of the Bone lab in 2015 and became Professor for Molecular Bone Biology in 2018. Currently, her group is particularly interested in the interactions of bone with hematopoiesis and hormones, and studies the role of Wnt and BMP signaling.

Friday 10 June at 1.00 pm (BST)

Speaker: Professor Chris Barratt, University of Dundee

Title: Phenotypic screening to identify new candidates for male contraception

Abstract: Professor Barratt is Head of the Division of Post Graduate Medicine at the Medical School, Head of the Reproductive Medicine Group at the University of Dundee as well as a clinical scientist (Hon) with NHS Tayside. He graduated with an Honours degree in Zoology and then completed a Post Graduate Certificate in Education (University of Wales, Swansea). His PhD, also in Zoology, was under the supervision of Jack Cohen at the University of Birmingham.

Professor Barratt has been awarded a number of honours for outstanding contributions to the discipline e.g. Young Andrologist of the Year, the Professor Sir Robert Edwards keynote lecture at ESHRE. He was awarded a DSc from University of Birmingham and has a h index of 55. Professor Barratt is a Fellow of the Royal Society of Edinburgh. Professor Barratt is helping coordinate the Global Initiative on Male Reproductive Health.

Friday 17th June at 1pm (BST)

Internal Seminar Series

Tuesday 5th July at 1.00pm (BST)

Speaker: Professor Michelle McDonald, The Garvan Institute of Medical Research, Sydney, Australia.

Title: 'Osteomorphs and Osteoclast Recycling: Intravital Imaging Reveals Mechanisms Behind Denosumab Withdrawal Induced Bone Loss'.

Venue: Lecture Theatre 3, F Floor Medical School.

Abstract: Osteoclasts are long lived highly specialised bone resorbing cells which form through the fusion of mononuclear pre-cursor cells and are believed to follow a linear fate and undergo apoptosis at the end of their life cycle. A number of anti-resorptive therapeutics target these cells, either preventing their resorptive function, Bisphosphonates, or inhibiting their formation, Denosumab (Anti-RANKL). These agents have achieved great success in preventing bone loss and fractures in patients with osteoporosis, amongst other diseases, however complications from their long term use has led to treatment cessation. In the case of Denosumab, treatment cessation has led to rebound bone loss and increased fractures, providing new challenges for its use in the clinic. We visualised the dynamics of osteoclasts in real time within live bone tissue leading to the discovery of a new fate for these complex cells. Further, this novel cell biology provides an improved understanding of patient response to anti-resorptive therapy.

We developed a novel intravital imaging methodology to visualize osteoclast dynamics on the intact endocortical surface of tibia in live mice. Employing a double reporter mixed bone marrow chimera model and using sRANKL to stimulate osteoclasts and osteoprotegerin-Fc (OPG:Fc) to mimic Dmab we examined osteoclast dynamics and function. We showed that in addition to apoptosis, osteoclasts undergo fission to form osteomorphs, a novel intermediate cell of the osteoclast lineage. These osteomorphs were then shown to re-fuse, confirming that the process of osteoclast recycling as an alternative cell fate to apoptosis. Using RNAseq we defined the osteomorph as a novel cell population, distinct from osteoclasts and osteoclast pre-cursors. Interestingly, osteomorph specific genes were associated with bone phenotypes in mice. We also showed accumulation of osteomorphs and their rapid re-fusion following withdrawal of OPG:Fc, providing a mechanism for the rapid bone loss and fractures suffered by patients following Denosumab withdrawal.

Friday 15th July at 1pm (BST)

Internal Seminar Series

Virtual Sheffield Paediatric Endocrine Teaching - ViSPET

Our departmental Paediatric Endocrine Teaching will usually take place on the 2^nd Monday (15:00) and 4^th Wednesday (16:00) of the month. 

Please click on the topic to access the live and recorded presentations. 

Past recorded webinars

Date	Time	Topic	Speaker
11/05/2020	1500	CAH - management aspects in the UK and beyond	Nils Krone - Sheffield
27/05/2020	1600	Thyroid - Stuff I have learned	Tim Cheetham - Newcastle
08/06/2020	1500	Turner syndrome	Alan Rogol - University of Virginia
24/06/2020	1600	Genetics of pituitary disorders	Mehul Dattani - London
13/07/2020	1500	Neonatal hypoglycaemia and Congenital hyperinsulinism	Senthil Senniappan - Liverpool
22/07/2020	1600	Management of patients with Prader Willi syndrome	Guftar Shaikh - Glasgow
10/08/2020	1500	The expanding spectrum of inherited adrenal insufficiency	Louise Metherell - London
26/08/2020	1600	Hypophosphatemic rickets	Nick Bishop - Sheffield
14/09/2020	1500	New treatments for bone disease	Paul Arundel - Sheffield
23/09/2020	1600	Diagnosis and management of rare diabetes	Tim Barrett - Birmingham
12/10/2020	1500	Endocrine management of Late Effects	Paul Dimitri - Sheffield
		ESPE CONNECT ONLINE 06/11 - 14/11/2020
25/11/2020	1600	Diagnosis and management of hypogonadism	Faisal Ahmed - Glasgow

For questions and suggestions, please contact Nils Krone (n.krone@sheffield.ac.uk)