Friday 31 January 2014

POSTGRADUATE OPEN DAY 5 February 2014

                               

 

The University is expecting over 650 prospective postgraduate students to campus next month at the event aimed at those who want to find out more about postgraduate study opportunities at Newcastle.

 

The event has been promoted widely around the city; on external PG websites and across campus; through the University's Careers Service and Alumni, social media and news channels, and invitations have been sent to over 10,000 prospective students (Newcastle's own undergraduates, alumni, enquirers, and attendees at the Russell Group PG Study Fairs).

 

The programme includes a series of presentations on postgraduate study and funding, campus tours, a subject information fair and School based activities. 

 

Further information about the PG Open Day is on the website or contact the team

 

 

Jobs: Postdoctoral Research on the SYBIL Project

Salary: £28,132 - £29,837 (with progression to £31,644)
Closing Date: 13 February 2014

You will investigate the mechanisms of long bone growth and characterise pathogenetic mechanisms in human genetic bone diseases.  You will be based within the Institute of Genetic Medicine (IGM) under the direction of Professor Michael Briggs and be working in close collaboration with other colleagues within IGM and the Institute of Cellular Medicine (ICM).


You will have a PhD in biochemistry, cell biology, molecular biology or a related area. You will have a proven track record of research in the area of in vivo genetic models and/or cartilage pathobiology to join this project within a new EU Frame Work 7 Programme "Systems Biology for the functional validation of genetic determinants of skeletal disease".


You should have advanced experience in studying mouse models of human genetic bone diseases and will have or obtain a personal licence to work with mice. It is also desirable to be proficient in histology, immunohistochemistry and biochemistry of cartilage, and also in proteomics (mass spec) and transcriptomics (microarray).


Informal enquiries should be directed to Professor Michael Briggs (michael.briggs@ncl.ac.uk).


Additional Website Links

 
 


Job Details



INE Seminar, NEXT THURSDAY, Feb. 6th: Prof. Sara Rankin "Pharmacological strategies to mobilize stem cells from bone marrow'

Just to remind you that next Thursday, 6th Feb. at 5pm (refreshments available from 4.30pmin room 2.21 of the Research Beehive, Newcastle University 

 

Prof. Sara Rankin  from Imperial College, London will be speaking on:

 

"Pharmacological strategies to mobilize stem cells from bone marrow."

 

 

 

Thursday 23 January 2014

Proteins and PSS

Proteomic analysis of pooled blood serum samples to detect symptom-specific changes in primary Sjögren's Syndrome patients

 

Katherine James 1,2, Simon J Cockell 3, Colin S Gillespie 4, Anil Wipat 2, Jennifer Hallinan 2, Benedikt M Kessler 5, Roman Fischer 5, Simon J Bowman 6, Bridget Griffiths 7, UKPSSR Study Group 8

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University,

3 Bioinformatics Support Unit, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University,

4 School of Mathematics and Statistics, Faculty of Science Agriculture and Engineering, Newcastle University,

5 Wellcome Trust Centre for Human Genetics and Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford,

6 Rheumatology Department, University Hospital Birmingham (Selly Oak), Birmingham,

7 Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne,

8 Institute of Cellular Medicine, Newcastle University

 

Objectives: Primary Sjögren's Syndrome (pSS) is a chronic autoimmune disease characterised by a range of symptoms including dryness, fatigue, depression, anxiety, pain and an increased risk of lymphoma. Patient populations are heterogeneous in their symptoms, making the accurate identification of pSS biomarkers non-trivial. This study aims to identify symptom-specific changes in protein abundance using serum samples from the UK Primary Sjögren's Syndrome Registry (UKPSSR), a cohort of clinically well-characterised pSS patients and healthy controls.

 

Methods: Patients were chosen from the UKPSSR database and grouped based on their levels of dryness, fatigue, depression, anxiety, and pain. Serum samples from each subject group were pooled and analysed by LC-MS/MS analysis using a Thermo LTQ Orbitrap Velos. Bioinformatic analyses and statistical modelling were then used to characterise the proteins and identify relationships between protein abundance and symptom levels.

 

Results: A total of 107 proteins were found to have significant changes in abundance between patient groups (ANOVA p>0.05, based on analytical duplicates). The majority of these proteins were immunoglobulins and components of the complement and coagulation cascades. Statistical modelling indicated that several of these abundance changes correlated with symptom levels. In particular, decreases in immunoglobulin chain regions are associated with the high fatigue and high pain groups, while slight decreases in complement components C1R and C4A were associated with dryness.

 

Conclusions: Differences in blood serum abundance of several proteins can be detected between groups of pSS patients with heterogeneous symptom profiles. These observations suggest that specific proteins may be biomarkers for the individual symptoms of pSS. Future analysis on a patient by patient basis could potentially reveal symptom-specific bio-fingerprints for individual symptom profiles.

Ranked List of Candidate Genes Associated with PSS

Application of probabilistic functional integrated network analysis to the study of autoimmunity and primary Sjögren's Syndrome

 

Katherine James 1,2, Jennifer Hallinan 2, Anil Wipat 2, Wan-Fai Ng 1

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University

 

Objectives: The majority of experimental datasets can be represented as networks of parts and interactions. A network representation allows biological data to be represented in a manner that is both tractable for human visual study and computationally amenable. One of the most powerful approaches to the integration of heterogeneous data is the use of probabilistic functional integrated networks (PFINs), since these networks have statistical weights that indicate the level of confidence in the evidence for each interaction. The confidence weights allow the use of a variety of statistical algorithms that take these weightings into account. This study aims to integrate an immune-specific PFIN from a number of relevant experimental datasets and apply it to the study of primary Sjögren's Syndrome (pSS) and related diseases.

 

Methods: Functional interaction data were sourced from the BioGRID and InnateDB resources. Datasets were confidence scored using a metabolic pathway Gold Standard dataset derived from the BioSystems Database. The confidence scores were integrated for each individual interaction using a weighted sum. The proteins of the network were then annotated using Gene Ontology biological process terms. Finally, the network was filtered to produce a sub-network of immune proteins and their high confidence interaction partners. The final network was assessed for its ability to predict known autoimmune disease-related proteins before being applied to the prediction of novel pSS-associated proteins and to the comparison of autoimmune diseases using a variety of network analysis techniques.

 

Results: A probabilistic functional integrated network of immunity was produced. The core immune PFIN contained ˜1700 proteins which were involved in >10,000 interactions. Clustering of the network based on interaction confidence revealed distinct patterns of interaction between pSS-associated proteins and several biological processes, in particular the stress responses. In addition, a ranked list of candidate pSS-associated genes was produced.

 

Conclusion: Probabilistic network analysis is a powerful approach to data integration and the study of human disease. The immune PFIN generated by this work provides a valuable resource for the future study of pSS and its comparison with other autoimmune diseases.

Wednesday 22 January 2014

Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis

Latest publication - see Arthritis Research & Therapy
Isaacs et al. Arthritis Research & Therapy 2013, 15:R204

http://arthritis-research.com/content/15/6/R204

Introduction

Our objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA).

Methods

Data of patients receiving tocilizumab or placebo in the MEASURE study were analysed. We investigated associations at baseline and during tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin, haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise in haemoglobin level.

Results

At baseline, CRP and haptoglobin were inversely correlated (modestly) with haemoglobin levels. After treatment with tocilizumab, CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2 weeks correlated with a week 12 rise in TIBC and haemoglobin.

Conclusions

Inflammatory anaemia improves in patients with RA treated with tocilizumab. This improvement correlates with the degree of suppression of systemic inflammation, reduction in hepcidin and haptoglobin and increase in iron-binding capacity. These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA.

REMINDER - MRG LAB MEETING 24.1.14

The MRG Lab Meeting will take place in the Seminar Room of the Baddiley Clark Building on Friday 24th January 2014 at 9.00 am.
 
Chair
 
Shane Walsh (PhD Student – PI Mark Birch)
 
Speakers
 
Rodolfo Gomez (Post Doc – PI David Young) Title of Talk - "Epigenetic control of MSC differentiation (Adipocytic and Osteoblastic fates)".
 
Siti Mohamad (PhD Student – PI Sophie Hambleton) Title of Talk - "Disease mechanism in novel disorder of lymphocyte apoptosis".
 
Fiona Gee (Post Doc - PI John Loughlin) - "Investigating the role of NCOA3 and SULF2 in osteoarthritis susceptibility"
 
 
 
 
 

Tuesday 21 January 2014

Bioinformatics & Systems Biology Seminar Series--David Martin, University of Dundee, 28 Jan@4pm

FMS BIOINFORMATICS & SYSTEMS BIOLOGY SEMINAR SERIES 2014

 

"Bioinformatics in the wild - understanding biology through new bioinformatics tool development"

Dr David Martin - University of Dundee

 

Tue 28 Jan @ 4pm, Research Beehive room 2.21

 

Biology has been changing dramatically over the last decades. We have moved from technically-challenging single gene studies which would define a career to high throughput data collection and interpretation. New technologies require new tools, and new technologies open up questions that were previously unanswerable. During this talk examples will be given of how a variety of new tools have contributed to key biological discoveries from the metabolism of Malaria, high throughput function prediction, phospho-proteomics in sleeping sickness and the challenges of genome assembly in plants.

 

How do we develop the skills to ask questions of a data rich science in the next generation of scientists? Dundee has undergone a complete renewal of its Life Sciences curriculum and new approaches to address data literacy in undergraduate and postgraduate courses have been implemented.  The impact of these changes on the student experience and learning outcomes will be discussed.

 

Faculty contact:  Diego Miranda-Saavedra (diego.miranda-saavedra@ncl.ac.uk), ext. 8590

Fibroblast Double Bill: More Details Wednesday 22 January 2014, 1.00pm



 

 

Institute Research Student Seminars

Speakers:  Nicola Green, PhD student (Transplantation) and

Rachel Williams, PhD student (Oral & Dental Sciences)

 

 

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

Date and time:  Wednesday 22 January 2014 at 1.00pm

 

 

Nicola Green will present:

 

"Fibroblasts as possible pro-inflammatory modulators in COPD".

 

This work evaluates the release of alarmins from lung epithelial cells in response to a variety of insults including oxidative stress, ER stress and viral infection and  their impact on lung fibroblast responses.  This is assessed in both primary "normal" lung cells and diseased primary cells extracted from explanted lung tissue from patients undergoing lung transplantaion for end stage COPD.

 

 

Key words:  COPD and Fibroblasts

_____________________________

 

Rachel Williams will discuss:

 

"Leptin-mediated MMP-1 production in gingival fibroblasts requires MAPK signalling".

 

Gingival fibroblasts secrete matrix metalloproteinases (MMPs) in response to inflammatory signals. I have previously shown that the adipokine leptin can regulate MMP production by primary human gingival fibroblasts, and this talk will discuss an intracellular mechanism that regulates this effect.

 

 

Key words: fibroblasts, inflammation, adipokines

 

Chair:  Darren Johnson, PhD student (Dermatology)

 

 

 

 

 

 

Tolerance, Immunity and Inflammation, Andrew Mellor

Diary Date: Institute Seminar:

 

“Pivotal pathways controlling the balance between tolerance and immunity at sites of inflammation" Professor Andrew Mellor and Dr Lei Huang.

 

Wednesday 26th February 2014 at 4.00pm.

Dental lecture theatre E, ground floor, Dental School

Fibroblast Double-Bill

Institute Student Seminar: Seminar room L2.5, 2nd floor, Leech Building, Medical School.
Wednesday 22 January 2014 at 1.00pm
·        Nicola Green "Fibroblasts as possible pro-inflammatory modulators in COPD"
·        Rachel Williams "Leptin-mediated MMP-1 production in gingival fibroblasts requires MAPK signalling"
Chair Darren Johnson (Dermatology)

Monday 20 January 2014

The Ageing Research Website

Did you miss this piece on the Musculoskeletal Research Group on the Biomedical Research Centre website?

http://www.ageingresearch.org/brc-home/our-achievements/advancing-medical-research/


12th International Sjogrens Syndrome Society Abstract - Japan

Integration of gene expression data with functional interaction and annotation data reveals patterns of connection between pSS-associated genes and the cellular processes in which they are involved

 

Katherine James 1,2, Jessica R Tarn 1, Shereen Al-Ali 1, Jennifer Hallinan 2, David A Young 1, Wan-Fai Ng 1

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University

 

Objectives: There is considerable discordance in data from different gene expression studies of primary Sjögren's Syndrome (pSS). Combining these data with other types of information, such as functional interactions and annotation data, can provide a more complete view of the cell in order to identify the key genes and biological pathways that are involved in the disease process of pSS.

 

Methods: In this study, a list of genes, found to be differentially expressed between pSS patients and controls in four large-scale microarray studies, was derived from the literature. The enrichments of Gene Ontology (GO) biological process annotations for this list were calculated in order to identify those processes that may be involved in pSS pathogenesis.

 

BioGRID is a comprehensive and highly-curated resource for functional association data generated by multiple experimental techniques. Using BioGRID data, a functional interaction network was generated in which nodes represented genes or gene products, and edges represented any type of BioGRID interaction between the nodes. The network was visualised using the Cytoscape visualisation platform and further annotated based on the Gene Ontology enrichment results. Finally, the network was filtered to produce sub-networks of pSS-associated genes.

 

Results: Following filtering, a total of 99 of the pSS-associated genes were involved in 111 interactions in the sub-network, the majority of which were connected in one component of 88 genes. All four gene expression datasets were represented within this connected component. Several tight clusters between genes annotated to the processes "innate immune response", "multi-organism process", "response to virus" and "response to stress" were observed in the integrated network. The sub-network also revealed patterns of interaction between these clusters and the pSS-associated genes. In addition, a large number of the pSS-associated genes were found to be annotated to these GO biological processes.

 

Conclusion: Gene enrichment and network analyses of the pSS-associated genes suggest that the innate immune responses, multi-organism processes, and the responses to virus and to stress are likely to be involved in pSS pathogenesis. Integration of multiple types of data in this manner can aid in the interpretation of results since combining diverse data sources reveals global properties not evident from a single data source. Future studies may benefit from incorporating additional detailed clinical data during the analysis of expression data in order to elucidate the relationship between gene expression and clinical phenotype.

Tuesday 14 January 2014

ICM students' seminar, Wednesday 15 January 2014, 1.00pm, Room L2.5, 2nd floor, Leech Bldg, Medical School

 

 

 

Institute Research Student Seminars

Speakers:  Laura Corbett, PhD student (Liver), Jonathan Richardson, PhD student (Pharmacology & Toxicology) and Dr Fiona Smith, Research Associate (Newcastle Magnetic Resonance Centre)

 

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

Date and time:  Wednesday 15 January 2014 at 1.00pm

 

Laura Corbett will present:

 

“Wnt Signalling and Hepatic Stellate Cells”.

My project explores how the Wnt signalling pathway influences the behaviour of hepatic stellate cells in liver fibrosis with particular focus on the contribution of canonical vs non-canonical Wnt signalling.

Key words:  Fibrosis, Wnt Signalling

_____________________________

Jonathan Richardson will discuss:

 

“Generalisability of pregnancy pharmacovigilance data”.

 

This presentation will briefly introduce some of the key pharmacoepidemiological techniques employed in teratogen surveillance, and examine limitations in their methodologies which impact on the extrapolation of study results to the general pregnant population.

 

Key words: Pregnancy, Pharmacovigilance, Teratogen

_____________________________

Dr Fiona Smith will speak on:

 

"Diurnal variation of skeletal muscle and liver glycogen concentration in healthy subjects

and well controlled type 2 diabetes".

 

Skeletal muscle plays a major role in glucose homeostasis. Meal carbohydrate is stored as glycogen in muscle and liver. Glycogen depots allow rapid storage of glucose. This mechanism has not been studied in Type 2 diabetes. Diurnal changes in skeletal muscle and liver glycogen concentration were compared in Type 2 Diabetes and healthy subjects.

 

Keywords:   Type 2 Diabetes, Liver and muscle glycogen, Magnetic Resonance Spectroscopy

 

Chair:  Sadaf Atarod, PhD student (Haematology)

 

 

 

 

 

 

 

Thursday 9 January 2014

Calling Laboratory Scientists

 

Reducing IrreProducibility in labOratory STudiEs
Connect with the NIHR Office for Clinical Research Infrastructure
Follow NOCRI on twitter: @NIHR_NOCRI


Calling all Laboratory Scientists

 

Reducing IrreProducibility in labOratory STudiEs: the RIPOSTE framework for improving the design and analysis of laboratory based research


The NIHR Laboratory Statistics Group is seeking laboratory scientists to be part of a consortium to test and refine a framework to reduce irreproducibility in laboratory studies. In particular we would welcome those with a relevant example study to share on the day (no examples involving animal experiments can be included).

What do we mean by 'laboratory study'?

1.     Studies in which any aspect of the procedure or analysis is carried out in the laboratory

2.     May be in vivo (e.g. imaging), ex vivo (e.g. genomics) or in vitro (e.g. cell culture)

3.     Includes both experimental and observational data

4.     May involve hypothesis generation or hypothesis testing/ confirmation

5.     May be small or large scale (e.g. genome-wide association studies)

We do not intend our recommendations will extend to exploratory research.

Your involvement
Involvement will include attending a one day meeting in Leicester on Monday 10 February 2014 where scientists will work together with statisticians to test and refine the framework. 

Register your interest
We are therefore seeking expressions of interest from laboratory scientists or researchers with experience in laboratory research to be part of this initiative.

Please register your interest at http://riposte.eventbrite.co.uk  by 15 January, 2014.
Respondents will be contacted by 17 January with further details.

Please can I ask you to forward this e-mail to relevant collagues who may be interested.

Best wishes,
Jennifer Cameron
Research Collaboration Manager
NIHR Office for Clinical Research Infrastructure (NOCRI)
www.nocri.nihr.ac.uk
NOCRI twitter

Registration site http://riposte.eventbrite.co.uk


DEADLINE for submitting Expressions of Interest: 15 January, 2014
 

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Institute Coffee Morning Friday 10-01-2014

Just a quick reminder that the first Institute Coffee Morning will be held tomorrow at 10am in the coffee room on 2nd floor Leech (on your right through the double doors from the lift).

 

Refreshments will be provided.

 

I look forward to seeing you there.

 

MRG LAB MEETING 10.1.14

The MRG Lab Meeting will be taking place in the Seminar Room of the Baddiley Clark Building on Friday 10th January 2014 at 9.00 am.
 
Chair
 
Michael Rushton (Post Doc – PI John Loughlin)
 
Speakers
 
Rachel Harry (Post Doc – PI John Isaacs) Title of Talk - "Cytokine Release Syndrome in response to antibody therapies in an ageing population"
 
Gary Reynolds (Wellcome Fellow – PIs Cat Hilkens/John Isaacs) Title of Talk - "The role of T cell derived GM-CSF in inflammatory dendritic cell generation in RA".