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

 

 

 

 

 

Best in the UK for student satisfaction

The 2014 National Student Survey has recognised the School of Biosciences as one of the very best places to study in the UK. The School was ranked first for Biochemistry, third for Biomedical Science, and ninth for Biology, with overall student satisfaction of 100%, 99% and 96% respectively. Our degrees also ranked first in individual categories of the survey, including teaching quality, academic support, personal development, and organisation and management.

Our students go on to become some of the country’s most employable graduates: we are placed in the top 20 for career prospects in the Guardian University Guide 2014. Coupled with Kent’s status as a top-20 university, this makes the School an excellent place to study the biological sciences.

 

Ebola: Progressing towards a cure

ebola virusDr Jeremy Rossman, School of Biosciences Lecturer in Virology, was recently interviewed on BBC Radio Kent about the deadly Ebola virus.

Western Africa is currently experiencing the world’s worst documented outbreak of the deadly Ebola virus, with over 1700 suspected cases and 932 deaths. Ebola is a highly pathogenic virus that can kill up to 80 % of the people it infects, though it is only spread by direct blood or bodily fluid contact.  Presently there are no approved vaccines or therapeutics for Ebola infection and current medical practice is limited to quarantine and supportive care.

Since Ebola virus was first discovered in 1976 there has been much research aimed at understanding the virus works and how it causes disease. However, this research has yet to translate into any licensed treatments because research on Ebola virus is hindered by safety concerns and a broad lack of funding.  Whilst, many laboratories can work with individual components of the virus, research on live virus is limited to a select few high-containment laboratories around the world.  Even for those select laboratories, there is a shortage of research funding as the virus is considered low risk and thus a low priority funding area for many developed counties.

Despite these limitations, there are currently several vaccines that have been developed that may prevent infection or mitigate the disease if given post-exposure. There are also multiple new therapeutic agents in various stages of development, including a treatment from the Canadian company Tekmira that has been undergoing initial human safety trials in the US.  It is unlikely that any of these vaccines or therapeutics will be ready for use during this current outbreak.  However, many developed countries are now questioning the risk Ebola virus poses and what can be done to enhance security.  With additional research funds, it is likely that we will have several vaccines or therapies available to treat Ebola virus infections in the decade to come.  These treatments may not completely cure the virus, but it may be possible to significantly reduce the loss of life in a future outbreak.

image of an Ebola virus by courtesy of Frederick A. Murphy and the US CDC