Sky TV features expert commentary on Ebola by Dr. Jeremy Rossman

ebola virusA recent commentary article by Dr Jeremy Rossman, Lecturer in Virology at the School of Biosciences, he warns that the situation could change if the ‘exponential’ spread of the disease in West Africa is not halted soon.

He commented: ‘The situation in West Africa continues to worsen as the largest Ebola virus outbreak continues to spread. Over 8000 people have been infected and there are now isolated cases in the USA and Europe. Current trends show an exponential increase in cases, with almost 35% of the new cases arising in the past 21 days. In Sierra Leone it is estimated that there are five new cases every hour. Despite the efforts of many countries, resources and experienced medical practitioners are in short supply. Without additional resources it will be extremely difficult to stem the spread of the disease.

‘Despite the dire situation, there is still only limited cause for concern within the UK. There is heightened security and screening intended to keep infected people from leaving the Ebola region and the NHS has prepared treatment and quarantine facilities in the event that a case does arise in the UK. Unfortunately, Ebola has a long incubation period which means that an infected person may pass all screening tests before becoming sick.

‘As a result, it is not possible to completely prevent Ebola-infected individuals from entering the county, as was recently seen in the USA. However, hospitals and clinicians have been trained to recognize Ebola and to initiate preventive quarantine and disease surveillance. Even if an isolated outbreak did occur in the UK, it is unlikely that the disease would spread, given the current health care system and our available resources. However, this situation could change if the exponential spread of Ebola virus in West Africa is not halted soon.’

Dr Rossman was recently interviewed by Sky TV, see the full interview here:

http://mms.tveyes.com/PlaybackPortal.aspx?SavedEditID=f63263a5-6a91-4078-8bf6-4d7c3817bd68

 

Research Seminar: Getting to know the enemy: The dastardly and conniving alpha-synuclein oligomer

Professor Daniel Otzen

Interdisciplinary Nanoscience Research Center (iNANO), Aarhus University

Wednesday 5th November, 4.00 p.m., Stacey Lecture Theatre 1

The 140-residue protein alpha-synuclein (aSN) is a key player in the development of Parkinson’s Disease, characterized by the death of i.a. dopaminergic neurons. Although natively unfolded as a monomer in solution, aSN readily forms amyloid fibrils which accumulate as intracellular inclusions. It is however increasingly accepted that the cytotoxic species are smaller oligomeric (non-fibrillar) states, which can disrupt phospholipid vesicles in vitro. The role of the oligomer in the aggregation of aSN is unclear. We have recently demonstrated that aSN can form oligomers of at least two different size classes. The smaller oligomer has a mean size of 430 ± 88 kDa or 30±6 aSN monomers. It consists of a dense core and a more extended or unfolded shell which is unable to elongate fibrils, but rather inhibits amyloid formation in a concentration-dependent way, consistent with an off-pathway oligomer [1]. Hydrogen-deuterium exchange mass spectrometry reveals that this oligomer in fact consists of two co-existing oligomer populations with different hydrogen-bond protection patterns. The majority species (75-80%) is only protected in the central part of the sequence and is not in exchange with monomers, while the minority species is more protected but likely exchanges through the monomer. We suggest that the minority species is on-pathway and can form fibrils by incorporating monomers, while the majority species is the cytotoxic off-pathway species [2]. Cytotoxic membrane permeabilization is inhibited by the plant compound EGCG (epigallocatechin gallate) by a mechanism that is rather unexpected: there are no changes in overall oligomer structure or size but the C-terminal tail, which is otherwise mobile, becomes relatively immobilized and the affinity for membranes is highly diminished [3].

References:

1.Lorenzen, N. et al. & Otzen, D. E. (2014). The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation. J. Am. Chem. Soc. 136, 3859-68.

2.Paslawski, W. et al. & Otzen, D. E. (2014). Co-existence of two different α-synuclein oligomers with different core structures determined by  Hydrogen/Deuterium Exchange Mass Spectrometry. Angew Chem Int Ed Engl Apr 16 (Hot Paper), [Epub ahead of print].

3.Lorenzen, N. et al. & Otzen, D. E. (2014). How epigallogatechin gallate can inhibit α-synuclein oligomer toxicity in vitro. J. Biol. Chem. In press (Paper of the Week).

 

Research Seminar: Datamining of bioactive ligands

Dr. John Overington, BSc PhD MBCS FSB FRSC C.Chem.

European Molecular Biology Laboratory – European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge

Wednesday 29th October, 4.00 p.m., Stacey Lecture Theatre 1

The ChEMBL database contains data from many successful and failed drug discovery projects. By querying the data in specific ways and performing data-mining, it is possible to discover useful rules for the selection of drug targets, rules for lead optimisation, and also for understanding and anticipating attrition during clinical development. During the talk we outline a number of examples of useful and practical rules discovered from the ChEMBL data, covering attrition and polypharmacology, screening file enrichment, and finally how to discover tractable targets from genomic and clinical data.

Research Seminar: Challenging clonal, uniparental inheritance of animal mtDNA.

Dr. Emmanuel (Manolis) Ladoukasis Department of Biology, University of Crete

Wednesday 22nd October, 4.00 p.m., Stacey Lecture Theatre 1

During ’90s animal mitochondrial DNA (mtDNA) was described as short, maternally inherited, non-recombining genome. Two decades later there is enough evidence to challenge these assumptions. In this talk I will present data, which show that both the maternal inheritance and the non-recombination of mtDNA might not be as strict as was previously believed. I will also suggest a hypothesis which couples maternal inheritance of mtDNA with heteroplasmy and recombination.

Wain Medal Lecture: The Battle of the Sexes: how sex chromosomes influence human health and disease

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Dr. James Turner, Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London.

Wednesday 15th October, 5.00 p.m., Woolf Lecture Theatre, University of Kent

Free and open to all

Most people would readily accept that men and women are different. Although some of these differences, for example in anatomy and biochemistry, are obvious, others are less commonly appreciated. For instance, women suffer from rheumatoid arthritis more often than men, and conversely, men are more commonly diagnosed with autism than women. Why is this the case? The answer is that men and women differ fundamentally in their genetic make-up.

XY chromosomesGenes are carried on chromosomes, and most of these chromosomes are identical between the sexes. However, one particular pair of chromosomes, the aptly-termed “sex chromosomes” is not the same in men and women. Women have two copies of a long, gene rich chromosome called the X chromosome, while men have one X chromosome, and a second, gene-poor, wimpy chromosome called the Y chromosome. As well as influencing disease susceptibility, these sex chromosomes determine whether a human embryo will go on to develop as a boy or a girl, and they have an especially important role in male and female fertility during later life.

In this presentation, I will explain how and why sex chromosomes appeared in our ancestors, and the benefits and drawbacks that they have for human health. I will also discuss how research into sex chromosomes is represented in the popular media, and how cutting edge research on these unusual chromosomes is creating new potential disease treatments.

Biography:

James studied Medicine at University College London, during which he also carried out a PhD in sex chromosome genetics at the Medical Research Council National Institute for Medical Research, London with Paul Burgoyne. He subsequently worked as a junior physician at West Hertfordshire NHS Trust, before returning to NIMR London to continue his work on sex chromosome genetics as a postdoctoral scientist. He completed his postdoctoral training in the laboratories of Peter Warburton, Mount Sinai School of Medicine, and David Page, Whitehead Institute, USA, before starting his own research group at NIMR and becoming an honorary research associate at UCL in 2007. His research focuses on the evolution, cell biology and biochemistry of the sex chromosomes from a variety of organisms, including mammals, in order to understand how these chromosomes influence human health and disease.

Teaching Awards for staff in School of Biosciences

Staff in the School of Biosciences have been recognised at the University Teaching Awards ceremonyTeaching Prizes. Dr. Jeremy Rossman received the Sciences Faculty Teaching Prize from the Vice-Chancellor, Professor Dame Julia Goodfellow, for the development of novel approaches to teaching Virology. His work with final year students encourages them to engage with cutting edge literature, placing them at the centre of the discovery process and developing the critical evaluation skills that are essential in scientific research.

Capping an extraordinary year of achievement, Dr. Peter Klappa was presented with a special (and surprise!) award at the ceremony in recognition of his sustained excellence in teaching. As part of the 50th Anniversary celebrations that are commencing this academic year, Dr. Klappa was presented with the award by Pro-Vice-Chancellor Professor Chris Davies. It follows his award of a National Teaching Fellowship in July 2014.

Research Seminar: Endosomal traffic in S. cerevisiae provides insight into human diseases

Professor Nia Bryant, Department of Biology, University of York

Wednesday 15th October, 3.45 p.m., Stacey Lecture Theatre 1

The high level of evolutionary conservation of membrane trafficking pathways and molecular machinery that regulate them enables the use of yeast genetics to gain insight into perturbations that underlie human diseases. I will discuss how studies of endosomal trafficking in the yeast S. cerevisiaehave furthered our understanding of how insulin regulates glucose uptake into fat an muscle; a process that is defective in the disease states of insulin-resistance and Type 2 diabetes. I will also describe how we are using yeast to understand how mutations in a regulator of endosomal membrane traffic lead to a congenital form of neutropenia; in this case information gleaned from identification of mutations that underlie the disease are also helping us reveal hitherto poorly characterised functions of the endosomal system.

 

 

Research Seminar: MDM2/p53 inhibitors: A novel targeted treatment for Neuroblastoma.

Professor Deborah Tweddle, Newcastle Biomedicine, Newcastle University Wednesday 8th October, 4.00 p.m., Jennison Lecture Theatre

Neuroblastoma is one of the most difficult childhood cancers to cure. Around 50% of all cases have high risk disease (metastatic disease in a child over the age of 18 months or MYCN amplified disease) and < 50% of these will be long term survivors. New targeted, less toxic treatments and a better understanding of drug resistance are needed before these survival figures can significantly improve.

One targeted treatment which is currently undergoing clinical development are MDM2/p53 inhibitors which target the interaction between the p53 tumour suppressor protein and its negative regulator MDM2 so increasing p53 levels and leading to tumour cell death.

We have been investigating the role of p53 in neuroblastoma for many years and have reported predominantly upstream defects of the p53 pathway making MDM2/p53 inhibitors a suitable potential novel therapy for neuroblastoma. In this talk I will describe our pre-clinical studies with novel MDM2 inhibitors in neuroblastoma in addition to the well-studied Nutlin compounds and the potential clinical uses of these agents.

Research Seminar: Proteomics, epigenetics, antigenic variation and evolution of the nucleus

Professor Mark Field Division of Biological Chemistry and Drug Discovery, University of Dundee

Wednesday 1st October, 4.00 p.m., Jennison Lecture Theatre

The control of gene expression, and more significantly gene cohorts, requires tight transcriptional coordination and is an essential feature of probably all cells. In higher eukaryotes, the mechanisms used involve controlled modifications to both local and global DNA environments, principally through changes in chromatin structure as well as cis-element-driven mechanisms. Although the mechanisms regulating chromatin in terms of transcriptional permissiveness and the relation to developmental programmes and responses to the environment are becoming better understood for animal and fungal cells, it is only just beginning to become clear how these processes operate in other taxa, including the trypanosomatids. Recent advances in understanding this process in lower eukaryotes, how this can relate to disease and what it can tell us about the evolution of the nucleus will be discussed.

More details are at http://dl.dropbox.com/u/6701906/Web/Sites/Labsite/Welcome.html

 

Ribosome movement, information processing and the language of life

LeverhulmeLife requires information transfer from nucleic acids to proteins. This involves the physical movement of molecular decoding machines (ribosomes) along linear nucleic acid templates (mRNAs). Ribosome movement, information processing, and the resulting control of protein levels are inseparably linked key determinants of cell health and disease. Dr. Tobias von der Haar from the Kent Fungal Group in the School of Biosciences was recently awarded a Leverhulme Trust Project Grant to use both computational and experimental approaches for studying how coordinated ribosome movement on mRNA templates creates a functioning “language of life”.These investigations will shed new light on central biological information transfer processes, and will inform our ability to manipulate biological information transfer in synthetic biology applications.

http://www.leverhulme.ac.uk/awards/news_item.cfm/newsid/286