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.

Top ten in UK for internationally-recognised research excellence

9094480516_15224345a5The University of Kent School of Biosciences has consolidated its position as one of the strongest Biological Science departments in the UK in the most recent Research Excellence Framework (REF 2014). As measured by the proportion of the highest quality outputs – deemed 4* and 3* in the REF exercise – 88% of the School’s submitted research outputs were judged to be “world-leading” or “internationally excellent”. This has placed the School of Biosciences in the top 10 nationally.

As measured by the grade point average (GPA) that is widely reported in league tables, the School was ranked 23rd in the UK – equal with Queen Mary and King’s College London, and above prestigious institutions that include Bath, Warwick, Southampton, Durham, Nottingham and Essex.

The REF results cap an extraordinary year of success for the School of Biosciences. They follow our exceptional performance in the National Student Survey, which also placed the School in the top 10 for overall student satisfaction for all three of our degree programmes. These external measures of academic excellence confirm the School as a leading centre of discovery within the biological sciences in the UK.

Prof. Darren Griffin discusses avian genome evolution on Radio 4

Darren bird Prof. Darren Griffin took to the airwaves on the Today programme this week to discuss his team’s part in the multi-national “Avian Phylogenomics Consortium“, whose work was published in a special collection of articles published in the journal BMC Genomics.

The articles describe the identification and analysis of 45 avian genomes, and has revealed fascinating evolutionary insights. In particular, the work of Prof. Griffin and colleagues has revealed that the genome organisation of chicken and related species such as turkey has the closest genomic resemblance to avian dinosaur precursors; something to think about over the traditional Christmas lunch!

Prof. Griffin’s interview can currently be heard on BBC iPlayer; the interview starts at 53:40 minutes.

 

 

Research Seminar: Understanding cell shape: reconstituting the actin-membrane interace.

Dr. Jenny Gallop, Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge

Wednesday 17th December, 4.00 p.m., Stacey Lecture Theatre 1

Membranes are central organizing surfaces for signaling and actin polymerization in the control of cell shape and movement. My work uses artificial membrane systems and frog egg extracts in real time assays to delineate and reconstitute the biochemical events underlying the membrane-localized assembly of actin. By using PI(4,5)P2 containing supported lipid bilayers on glass we were able to form actin structures that resemble filopodia and show that they form by self-assembly of protein networks on a permissive membrane surface. By comparing the lipid specificities of actin polymerization from lipid bilayers of different curvature we have identified how signals from membrane curvature and composition can be combined to recruit different adaptor proteins during endocytosis, which then co-opt more general actin machinery. We are beginning to understand how the cell can form actin structures of different types within a common cytosol.

 SPONSORED BY CAIRN RESEARCH.

Review – Global Skills Award Lecture: Are our (genetic) male bits disappearing?

Professor Darren Griffin was the guest speaker at a lecture for postgraduate students enrolled on the Global Skills Award programme.

The lecture, entitled ‘Are our (genetic) male bits disappearing?’ was well received thanks to the fascinating subject and Darren’s friendly and humorous delivery. Even those from a non-biosciences discipline were interested in the ideas that were discussed and felt that they took a lot of information away with them.

“Professor Griffin made this into a very interesting topic of investigation. It was clearly structured and I could understand what he was talking about, even though I didn’t have any knowledge of this area prior to the lecture” – Psychology student

Darren initially looked at male and female traits, posing the questions, “Why do we need men?” and “Why do we have sex?” before giving a basic biology lesson on genomes and genetic exchange.

The main focus of the seminar however was on the (male) human Y chromosome and how it came to ‘shrink’.

Darren explained that a string of mutations caused by the absence of a ‘mutual support mechanism’ led to a structural differentiation between the X and Y chromosomes. In mammals, this involved a loss of DNA from the Y chromosome, the accumulation of ‘junk’ DNA and a reduction in genetic exchange.

This process continued until there was very little similarity between X and Y and only a small region of genetic exchange.

He then went on to discuss the ‘debate’ in the genome evolution community about whether or not the mammalian (including the human) Y chromosome would eventually disappear and when. He looked at two opposing theories by Jenny Marshall-Graves and Jennifer Hughes, given at the 18th International Chromosome Conference in Manchester on 31 August, 2011.

Darren closed the lecture by saying that the human Y chromosome has indeed shrunk considerably; but it has also evolved some clever mechanisms to ‘put the brakes on’.

Darren has always enjoyed giving the global skills lecture. He said: “It’s an important opportunity to get across work that we do in Biosciences in an accessible way to students with a range of backgrounds.  The programme is an exciting one and the audience is always receptive.”

What do you think? Did you attend the lecture last Monday? What did you make of the topic of the lecture?

Here are some more quotes from other postgraduate students that attended:

“He was able to simplify really complex material without losing the importance and the essence of it. It was a great lecture” – Law student

“Excellent. This lecture was one of the best I have seen in my academic career, so far. Funny, entertaining and interesting. An evening well spent!” – Business student

“Professor Darren Griffin executed the lecture with extreme confidence, humour and in-depth knowledge” – Biosciences student

Professor Darren Griffin

Professor Darren Griffin

 

 

Darren Griffin is a professor of genetics. You can read more about him and his research at http://www.kent.ac.uk/bio/profiles/staff/griffin.html.

Research Seminar: Modelling the Kinetics of Protein Polymerization in Amyloid Diseases

Dr. Marie Doumic, INRIA Rocquencourt, BANG project team, France

Wednesday 10th December, 4.00 p.m., Stacey Lecture Theatre 1

Amyloid diseases are of increasing concern in our aging society. They are a group of diseases which involve the aggregation and the deposition of misfolded proteins, called amyloid, which are specific for each disease (PrP for Prion, Abeta for Alzheimer’s). In a healthy state, they remain monomeric, but when misfolded they propagate the abnormal configuration and aggregate to others, forming very long polymers also called fibrils. Elucidating the intrinsic mechanisms of these chain reactions, most probably specific for each disease, is a major challenge of molecular biology: do polymers break or do they coalesce? Do some specific sizes polymerize faster? What is the size of the so-called nucleus, i.e. the minimum stable size for polymers? Does polymerization occur by monomer, dimer, or i-mer addition? On which part of the reactions should a treatment focus to arrest the disease? Up to now, only very partial and partially justified answers have been provided. This is mainly due to the extremely high complexity of the considered processes, which may possibly involve an infinite number of species and reactions (and thus, an infinite system of equations). Mathematical modelling, simulation and parameter estimation methods are thus required and already proved to have a major impact on understanding amyloids’ kinetics. In this talk I will review existing results and explain our approach, which is based on combined ODE-PDE (and more recently stochastic) models. I will also develop some of our recent findings, both in a mathematical and more general side, with some focus on specific applications for different proteins.

Cancelled – Research Seminar: Dissecting cancer heterogeneity

Dr. Florian Markowetz, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre

Wednesday 3rd December, 4.00 p.m., Stacey Lecture Theatre 1

I will talk about computational methods to address heterogeneity of breast and ovarian cancer at different levels:

(i) At the *population* level breast cancer appears in different subtypes and I will talk about our recent work on finding 10 different manifestations of the disease.

(ii) At the *patient* level, different cancer sites can differ significantly in the genomic aberrations they carry. I will discuss how to quantify intra-patient heterogeneity by rigorous analysis of multiple patient samples.

(iii) At the *sample* level we often find cancer cells mixed with immune cells, stromal cells and others. This mixture of cells leads to a mixture of signals when DNA, RNA, or proteins are measured in these samples. I will present an automated and quantitative approach that leverages image analysis of histopathological images to estimate cellular composition and complement genomic profiling.