Research Seminar: Perception of host imposed oxidative stress by the human fungal pathogen Candida albicans

Professor Janet Quinn, Institute for Cell and Molecular Biosciences, Newcastle University

Wednesday 4th March, 4.00 p.m., Stacey Lecture Theatre 1

Candida albicans is an important fungal pathogen of humans causing approximately 400,000 life-threatening systemic infections each year. Stress responses are essential for this fungal pathogen to evade host anti-microbial defence mechanisms and to survive rapidly changing microenvironments found within diverse host niches. We are particularly interested in the sensing and signalling mechanisms employed by C. albicans to perceive and respond to reactive oxygen species (ROS) encountered during infection. Upon contact with C. albicans, the NADPH oxidase complex in phagocytic cells produces high levels of superoxide which is rapidly converted to H2O2. To survive in the phagocyte C. albicans must mount a rapid transcriptional response to induce the expression genes encoding antioxidant and repair proteins. Furthermore, phagocytosis of C. albicans by macrophages, or exposure to ROS in vitro, initiates filamentous growth. In this talk I’ll highlight how oxidation of specific signalling proteins plays a key role in the perception and regulation of both transcriptional and morphogenetic responses to ROS in C. albicans. In addition, I’ll also describe some recent findings detailing mechanisms employed by the host to prevent the rapid oxidative stress responses needed for fungal survival.

Research Seminar: Engineering Polymeric Materials for Biomedical Applications

Dr. Theoni K. Georgiou, Department of Material, Imperial College London

Wednesday 25th February, 4.00 p.m., Stacey Lecture Theatre 1

My research activities that will be summarised during the seminar involve the fabrication of novel well-defined polymer and polymer based materials that find use in biomedical applications. For examples star polymers for gene delivery, injectable gels for tissue engineering and functional polymer conjugates for drug delivery or other type of therapy and imaging. All polymers are fabricated using a systematic approach in order to investigate how key polymer structure characteristics affect the polymer’s properties as well as their ultimate application.

Research Seminar: Redox-signalling mechanisms regulating growth, ageing and responses to stress.

Dr. Elizabeth Veal, Institute for Cell and Molecular Biosciences, Newcastle University

Wednesday 18th February, 4.00 p.m., Stacey Lecture Theatre 1

Reactive oxygen species (ROS), such as hydrogen peroxide, can cause lethal levels of oxidative damage. Indeed, oxidative cell damage is associated with a multitude of common diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases. There is a growing appreciation that, as well as activating endogenous ROS defences, low levels of hydrogen peroxide are used to regulate diverse processes, including cell division, differentiation and migration. ROS signals have even been shown to increase lifespan. However, the mechanisms that mediate these effects, or allow cells to differentiate between toxic and signalling ROS levels are poorly understood. I will describe how we have exploited the different advantages of yeast, nematode, cultured cell and mathematical models to provide some unexpected answers to these questions.

Research Seminar: Creating artificial blood?: Is the only way Hollywood or Essex?

Professor Chris Cooper, School of Biological Sciences, University of Essex

Wednesday 11th February, 4.00 p.m., Stacey Lecture Theatre 1

The red blood cell is one of the simplest mammalian cells and therefore one of the more accessible targets for an artificial synthetic biology approach. And the search for a blood substitute has long been a holy grail for transfusion scientists: a long-lasting virus free product would be able to reach the parts of the world the current blood supply cannot access. This complex research and clinical problem was recently solved by filmmakers keen to show that drinking synthetic blood enabled “vampires” to live in harmony with human beings. This talk will show how far (or near!) current research in this area is from the Hollywood reality.

New hope for understanding sudden cardiac arrest

Cover-e1421840532321-1024x681New biosciences research at the University could point the way to greater understanding of the heart mutations that cause sudden cardiac arrest.

Hypertrophic cardiomyopathy is a genetic condition that one in 500 people carry and is a leading cause of sudden cardiac arrest in young athletes. The footballer Fabrice Muamba famously collapsed during a match when his heart suddenly stopped. Although he was eventually resuscitated, he is now unable to play football competitively and has a chest implant to restart his heart.

Now a team led by Dr Neil Kad, Lecturer in Molecular Biophysics at the School of Biosciences, has managed to identify for the first time at the single molecule level how heart muscle is turned on and off by calcium.

By understanding how the heart is regulated by calcium, the research team has set the ground for greater insight into how the heart is affected when specific components are mutated during disease.

Using this new approach, the researchers were able to identify how the motors (myosins) within muscle talk to each other along the long protein tracks (thin filaments). They found that two motor heads are required to turn on a thin filament segment as regulatory unit. Once activated, this regulatory unit was found to be capable of accommodating 11 further myosin motors.

To date, all treatments for sudden cardiac arrest target the symptoms of this disease. The findings from this study are expected to provide new tools for research into treating the causes of the condition, rather than only the symptoms.

The research, titled Using Fluorescent Myosin to Directly Visualize Cooperative Activation of Thin Filaments (Dr Neil Kad, Professor Michael Geeves, University of Kent; and Rama Desai, Imperial College London) will be published in the 23 January issue of the Journal of Biological Chemistry, where it has been selected as paper of the week. For paper click here .

Research Seminar: The machinery of RNA degradation, processing and riboregulation in E. coli.

Professor Ben Luisi, Department of Biochemistry, University of Cambridge

Wednesday 4th February, 4.00 p.m., Stacey Lecture Theatre 1
Small regulatory RNAs enrich the network complexity of post-transcriptional gene control in prokaryotes. In bacteria such as Escherichia coli and Salmonella sp., the action of many small RNAs in silencing transcripts involves the endoribonuclease RNase E. The enzyme serves as the scaffold of a multi-protein assembly, known as the RNA degradosome, which plays a central role in many cellular RNA turnover and processing events.  We describe the organisation and cellular localisation of the degradosome. and we present a model for how some sRNAs act in conjunction with the RNA chaperone Hfq to guide the ribonuclease to cleave targeted transcripts.

Research Seminar: Modelling protein structure, function and disease variants

Professor Michael Sternberg, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London

Wednesday 28th January, 4.00 p.m., Stacey Lecture Theatre 1

This talk will describe computational tools we have developed for protein modelling.

 

Phyre2, primarily developed by Lawrence Kelley, is a widely used web server which takes a protein sequence and predicts a 3D structures based on coordinates of an homologous protein. Phyre2 includes the option PhyreAlarm which automatically notifies you if there is a new structure which yields a better model.

When in our group Mark Wass, developed tools to predict protein function from sequence (CombFun) and potential ligand binding sites (3dLigandSite).

Recently we have studied disease causing variants in protein. We showed that the interface between proteins is enriched in disease causing variants compared to the surface regions (Alessia David et al). We also identified that certain Pfam domains are more susceptible to disease than others, in part due to being hub proteins in the interactome. These concepts led to the development by Chris Yates of a web based algorithm SuSPect to predict the phenotypic effect of missense variants.  SuSPect is integrated into Phyre2. SuSPect combined with interactome data yields a powerful approach to prioritise genes with missence mutations that are associated with a particular disease.

Professor Michelle Garrett to Present Public Cancer Lecture

image MDG lectureKent Cancer trust has invited Professor Michelle Garrett from the School of Biosciences to present a public lecture on cancer research entitled:
‘Cancer research and treatment; past, present and future’

The date for the lecture is Wednesday 21st January at 19.00 in the Michael Berry Lecture Theatre (og46), Old Sessions House, Canterbury Christ Church University.

The lecture is open to all, everyone warmly invited to attend.

£3.5 million for ‘world leading’ bioscientists

Bioscientists at the University have been awarded nearly £3.5 million to research the production of bacterial cells with enhanced internal organisation for industrial biotechnological processes.

The research, led by Professor Martin Warren and his team in the School of Biosciences, is one of five projects to be recognised by the BBSRC (Biotechnology and Biological Sciences Research Council) as part of its Strategic Longer and Larger Grants (sLoLaS) scheme.

Professor Warren, who is receiving the largest grant (£3.484 million) among the five university beneficiaries, said that support for his research was ‘exciting’ and would help keep the University of Kent at the forefront of synthetic biology, resulting in strong interaction with industry.

For more information, please see the University of Kent’s press release.

Research Seminar: Transcription is essential for the establishment of sister chromatid cohesion on chromosomal arms

Dr. Monika Gullerova, Sir William Dunn School of Pathology, University of Oxford

Wednesday 21st January, 4.00 p.m., Stacey Lecture Theatre 1

Cohesin is a multi-subunit protein complex essential for sister chromatid cohesion, gene expression, recombination and DNA damage repair. The underlying determinant of cohesion establishment on chromosomal arms remains enigmatic. We have successfully applied single-locus specific DNA-FISH to study cohesion dynamics in vivo, and show that topologically bound cohesive cohesin coexists with its loader Mis4Scc2-Ssl3Scc4 in fission yeast. In contrast, cohesin independent of its loader is unable to maintain stable cohesion. Cohesive sites overlap highly expressed genes and transcription inhibition reduces chromatin association of cohesion proteins. Reciprocally, heat shock induction leads to de novo recruitment of cohesive cohesin. Furthermore, cohesin and its loader physically interact with RNA Polymerase II. Finally, we show that transcription facilitates cohesin loading to chromatin in budding yeast and human cells. We suggest that transcription is the key determinant of cohesive sites on chromosomal arms in eukaryotes.