Tuesday 28 October 2014

From Oestrogen Receptors to Ageing Brains



Institute Research Student Seminars

Speakers:  Stephanie Meyer & Elizabeth Dutton


Venue: Seminar room L2.5, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 29th October 2014 at 12.30


Stephanie Meyer will present:


"Effect of oestrogenic chemicals on the liver"


The oestrogen receptors (ERs) are a major target for endocrine disruptor chemicals which can affect health and reproduction by disturbing the hormone system in animals and humans. The commonly used food colour tartrazine has previously been shown to activate the human ERα in vitro and caused a cholestatic liver injury when injected into mice intraperitoneally. Therefore tartrazine was examined for its ability to activate the mouse oestrogen receptors and its potential to cause adverse effects when administered orally in an experimental mouse model was investigated.



Key words:  Oestrogen receptors, xenoestrogens, cholestatic liver disease



Elizabeth Dutton will discuss:


"Use-it-or-lose-it" - Older adults' perceptions of brain health and its maintenance"


Physical activity is associated with a reduced risk of dementia. However, health messages have limited impact on physical activity levels amongst older adults. A design-research workshop explored perceptions of brain health with eight older adults, and what actions, if any, people undertake to maintain their brain health. The research forms part of a PhD research project to design products and services to engage people in physical activity to improve brain health.



Key words: Physical activity, brain health, dementia




Chair:  Rebecca Brennan







Thursday 23 October 2014

Immunology NE Thursday 6th November: Human Dendritic Cell Subsets

INE for November will take place at 4pm (refreshments from 3.30pm) on the 6th November in Lecture Theatre D of the Dental School, Newcastle University. Please note a change to the usual time and place.

Dr Elodie Segura will present a talk entitled "Functional specialization of human dendritic cell subsets".

After completing a PhD on the immune functions of dendritic cell-derived exosomes in 2006 at the Institut Curie under the supervision of Clotilde Théry, Elodie Segura was a post-doctoral fellow in the laboratory of José Villadangos at the Walter and Eliza Hall Institute (Melbourne, Australia) working on the functional specialization of murine DC subsets (2006-2009). From 2010, she was a senior post-doctoral fellow in the laboratory of Sebastian Amigorena at the Institut Curie where she developped human DC subsets studies. She was recruited as "Chargé de Recherche" (permanent position) in 2012. She was the laureate of the 2012Biolegend "Young Investigator Award" awarded by the European Federation of Immunological Societies.

Some of Elodie's recent publications can be found below:
Segura E, Valladeau-Guilemond J, Donnadieu M-H, Sastre-Garau X, Soumelis V, Amigorena S.(2012).Characterisation of resident and migratory dendritic cells in human lymph nodes. J Exp Med. 209(4) : 653-60.
Segura E, Touzot M, Bohineust A, Cappuccio A, Chiocchia G, Hosmalin A, Dalod M, Soumelis V, Amigorena A (2013). Human inflammatory dendritic cells induce Th17 differentiation. Immunity 38(2):336-48. Segura E, Durand M, Amigorena S (2013) Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells. J Exp Med 210(5):1035-47.Segura E, Amigorena S (2013). Inflammatory dendritic cells in mice and humans. Trends Immunol. 34(9):440-5.Segura E, Amigorena S (2014). Cross-presentation by human dendritic cell subsets. Immunol letters. 158(1-2):73-78.

'The Regulation of Cartilage Tissue Catabolism by the Endocytic Receptor LRP1'' Dr Kazuhiro Yamamoto


Speaker: Dr Kazuhiro Yamamoto, Kennedy Institute of Rheumatology, University of Oxford


Venue: Room L2.6, William Leech Building, Medical School

Date and time: 10-11am Friday 24th October 2014


Dr Kazuhiro Yamamoto will present:

‘’The Regulation of Cartilage Tissue Catabolism by the Endocytic Receptor LRP1’’



Cartilage degradation in osteoarthritis (OA) is now well established to be the result of elevated proteinase activities, with the key enzymes being aggrecanases and collagenases. Aggrecanase activities are post-translationally regulated by prodomain removal, C-terminal processing and inhibition by the endogenous inhibitor, tissue inhibitor of metalloproteinases (TIMP)-3. My recent study showed that low-density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic process is also an important regulator of aggrecanases (ADAMTS-4 and ADAMTS-5) and collagenase 3 (MMP-13), in normal healthy cartilage. However, this process is impaired in OA cartilage due to increased shedding of LRP1, which results in increased extracellular activities of aggrecanases and MMP-13. I will talk about how I discover the novel endocytic pathway and its impact on cartilage tissue catabolism. I will also focus on my current and future approaches to investigate how tissue maintains extracellular matrix homeostasis by controlling tissue-degrading proteinases and how tissue loses the homeostasis with ageing and pathological conditions.


Key words:

Tissue catabolism; Osteoarthrits; Endocytosis; Extracellular trafficking; Metalloproteinases.


Tuesday 21 October 2014

The Regulation of Cartilage Tissue Catabolism by the Endocytic Receptor LRP1

Friday 24th October 2014 - Room L2.6, Leech Building, Medical School 10-11am
Dr Kazuhiro Yamamoto will give a seminar entitled 

"The Regulation of Cartilage Tissue Catabolism by the Endocytic Receptor LRP1"


Variety: Sinusitis, fibrosis, inflammation, Bioinformatics, sensor, Clostridium difficile, Eczema, Filaggrin, Methotrexate




Institute Research Student Seminars

Speakers:  Stephen Ball, Beth Lawry & Martina Elias


Venue: Seminar room L2.5, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 22nd October 2014 at 12.30


Stephen Ball will present:

“Epithelial – Fibroblast interactions in the pathogenesis of chronic rhinosinusitis”


Chronic rhinosinusitis (CRS) is one of our commonest health conditions, affecting up to 12.5% of adults, is the fifth commonest antibiotic prescription and incurs $5.8billion in direct health costs.  Maximal medical therapy (antibiotics/steroids) has high failure rates and as a result 1 in 4 patients undergo surgery, though this is not surprising given the pathogenesis of CRS is not known.  Here we are investigating the roles of the epithelium & fibroblasts in the persistent inflammatory processes.


Key words: Sinusitis, fibrosis, inflammation


Beth Lawry will discuss:

Characterising Unique Detection Biomarkers for Clostridium difficile”


Using a novel bioinformatics system, unique Clostridium difficile biomarkers were identified and confirmed with laboratory techniques. Antibodies against these markers will be integrated into a detection sensor.


Key words: Bioinformatics, sensor, Clostridium difficile


Martina Elias will speak on:

Mechanistic insights into methotrexate efficacy in eczema”


Null mutations in the key epidermal protein, Filaggrin, strongly predispose the development of Atopic Eczema (AE). Methotrexate is an effective therapeutic option; however, its precise mechanism of action in AE is unknown. We have shown MTX acts directly on keratinocytes to promote epidermal differentiation, lipid accumulation and improved barrier function in a thymidine dependent manner. A detailed understanding of these mechanisms may ultimately reveal novel therapeutic targets for the treatment of AE and other disorders of keratinisation.


Keywords: Eczema, Filaggrin, Methotrexate


Chair:  Sophie Cassidy





Wednesday 15 October 2014

Today's Student Seminar @ 12:30




Institute Research Student Seminars

Speakers:  Katie Griffiths, Hanan Kashbour & Intan Abd Hamid


Venue: Seminar room L2.5, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 15th October 2014 at 12.30


Katie Griffiths will present:


Laser-scribed graphene: a genuine contender for point of care diagnostics?


Graphene’s unique combination of properties owing to its 2D structure makes it very popular in many research areas. A new method utilising LightScribe disc labelling technology has demonstrated a simple, inexpensive solution to production of this material. The electrochemical behaviour of Laser-scribed graphene out-performs the gold standard of carbon electrodes, yet offers a more affordable, scalable manufacturing process. Such material is amenable to numerous point-of-care biological assays including enzyme based glucose sensors.


Key words: Biosensor, point of care diagnostics, grapheme


Hanan Kashbour will discuss:


An investigation of the molecular and the structural features of transverse tubule development in cardiac muscle.


Transverse tubules are invaginations of the plasma membrane of cardiomyocytes facilitating rapid transmission of electrical action potentials throughout the cell and contribute to the process of excitation-contraction coupling (EC coupling).  Alterations in t-tubule conformation have been reported in heart failure (HF) and suggested to contribute to the impairment of EC coupling.  It is important, in order to offer clues for possibly correcting the cardiomyocyte abnormalities of HF, to understand the mechanisms involved in determining normal t-tubule structure and function. My project will examine the changes in cardiomyocyte structure (by transmission and scanning electron microscopy) occurring during development (in utero and post-natally) to adulthood. This will allow the assessment of t-tubule formation in relation to other important cardiomyocyte specialisations (z-lines, sarcomeric myofilament spacing, sarcoplasmic reticulum and mitochondria). 



Keywords: T tubules, EC coupling, Cardiomyocyte



Intan Abd Hamid will speak on:


Long-term outcome of SCID patients who had underwent Hematopoeitic Stem Cell Transplantation


Severe Combined Immunodeficiency Disorder is a rare disease affecting 1 in 100,000 children.  It is considered one of the paediatric emergencies and most patients do not reach their 1 year old birthday if untreated. The focus of my research is to explore the long term outcomes of those who have been transplanted and how issues such as donors selection, conditioning regime, choices of stem cell source and genotype-phenotype association influence the outcome.


Keywords: Severe Combined Immunodeficiency Disorder (SCID), Hematopoeitic STem Cell Transplantation (HSCT), Long-term Outcome



Chair:  Anna-Lena Dittrich








Tuesday 7 October 2014

Osteoblasts and Osteoarthritis, Myofibroblasts and Renal Fibrosis





Institute Research Student Seminars

Speakers:  Dimitra Tsompani & Lotfia Nawafa


Venue: Seminar room L2.6, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 8th October 2014 at 12.30


Dimitra Tsompani will present:


"The Role of Histone Deacetylase 3 in Chondrogenesis and Osteoarthritis"


Histone deacetylases (HDACs) regulate the acetylation pattern of chromatin to control gene expression and determine cell differentiation and mammalian development. Our aim is to examine the ability of a broad-spectrum of HDAC inhibitors and a HDAC3- targeting small interfering RNA (siRNA) to protect against cartilage degeneration in vivo and in vitro and to investigate the role of HDAC3 loss in chondrogenesis differentiation using human mesenchymal stem cells. In this way we hope to achieve a better understanding of the potential role of HDAC3 in the development and/or progression of osteoarthritis (OA).


Key words: HDAC3, Osteoarthritis, Chondrogenesis


Lotfia Nawafa will speak on:


"The Contribution of Methyltransferase SET9 in Renal Fibrosis"


The essential role of TGF β-1/SMAD signalling in stimulating fibrogenic cells to produce ECM proteins and promoting proliferation of  Myofibroblasts is widely recognised. SMAD3 is known as a mediator in TGF β- 1-induced fibrosis in the kidney.


SET9, a methyltransferase enzyme that specifically methylates histone 3 at lysine 4 position, is shown to play a central role in regulating SMAD3 activity, as shown by SET9 knockdown. The overexpression of wild type SET9 results in increased SMAD3 activity, specifically in the presence of TGF β-1. Conversely, expression of a mutant SET9, which lacks methyltransferase activity, failed to increase SMAD3 activity, even in the presence of TGF β-1.



Keywords: TGFB-1 pathway,SMAD3,SET9


Chair:  Cecilia Jimenez Moreno







Thursday 2 October 2014

MRG Lab Meeting October 3rd: Osteoarthritis Special

Kath Johnson (PhD Student - PI John Loughlin) Title of Talk – "Functional analysis of the osteoarthritis susceptibility locus marked by the polymorphism rs10492367"
Carole Proctor (Lecturer) Title of Talk – "Investigating mechanisms of osteoarthritis with computer simulation models"
Angie Habgood (PhD Student – PI Drew Rowan) Title of Talk – "The effect of tissue specific chondroprotection on remodelling events in bone and cartilage in health and disease"