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Postdoctoral research opportunities

We are seeking candidates who are internationally competitive, taking into account the current stage of their career.
The strongest candidates may be offered a short term departmental fellowship during which time they would be expected to seek external funding. We will provide other candidates with help in applying for appropriate fellowships that can be hosted at QMUL.

Current available projects in the School of Biological and Chemical Sciences - please follow the project title link to find out details and contacts.

If you would like to apply for one or more projects, contact the PI with attaching a CV and two paragraphs describing your relevant background. More details might be obtained from the PI if required.

Biological and experimental psychology:

Ecology and behavioural biology:

Evolutionary and organismal biology

Mechanistic and structural biology:

Synthetic chemistry:

Materials chemistry and interfaces:

 

Communication, cognition and welfare in mammals - Alan McElligott

Potential research projects exist that examine communication, cognition in mammals (in particular, ungulates), and how these affect animal welfare. Key to this research is to consider the evolutionary history of a species, individual differences in temperament, and how the domestication process may have affected communication behaviours. One of the most important research areas to be considered is how communication and recognition between mothers and their offspring develops.

Understanding the interaction of Nedd4-family ubiquitin ligases with their substrates - James Sullivan

Ubiquitin is a highly conserved small protein, which can be covalently linked to other proteins leading to their sorting, often to a degradatory complex or compartment. Ubiquitination involves a sequential cascade of reactions the last step of which is mediated by ubiquitin ligases, which control substrate specificity. A huge number of proteins have been shown to be ubiquitinated and it is clear that ubiquitination is a post-translation modification as important as phosphorylation.

One highly conserved group of ubiquitin ligases are the Nedd4-family. These enzymes perform a regulatory role in numerous cellular processes, from ion transport in yeast to neural development in Drosophila. Nedd4 ligases bind to short “PY” motifs in their substrates through “WW” domains in the ligase. Nedd4 ligases contain between 2 and 4 WW domains and some substrates have up to six PY motifs. In recent years it has become apparent that multiple interactions take place between Nedd4 ligases and their substrates, but the reason for this is at present unclear.

The aim of this project is to investigate in detail the interaction between Nedd4 ligases and their substrates. The project will initially utilise two ‘model’ ligases, the archetypal human Nedd4 ligase and the yeast ligase Rsp5. The project will involve using in vitro biochemical assays with recombinant proteins and in vivo imaging techniques with human cell lines and transgenic yeast to clarify what interactions take place between Nedd4 ligases and their substrates and for what purpose. 

The statistical analysis of spatial genetic data - Richard Nichols

It is a fundamental observation that that allele frequencies in almost every species differ from place to place. These data can yield crucial insights into the species' biology – ranging from the parts of the genome that have been affected by selection on the one hand, to the historical change in the species' distribution on the other. The most widely used methods for analysing these patterns do not make full use of the combined genetic and spatial data for independent loci, let alone the effects of recombination between more closely linked loci. This type of problem will become more and more important as the new sequencing technologies provide whole-genome sequence from multiple individuals in different geographical locations. This project will implement and test methods to deal with this new type of data. Since this research is at the intersection of Statistics and Genetics it would suite a postdoctoral researcher from either discipline. For example a statistician interested in moving into Genetical problems (say with experience of Bayesian analysis or Generalized Linear Mixed Models) or a Geneticist with an interest in moving into cutting edge statistical analysis. Applicants with other relevant backgrounds are welcome.

Catalysis, coordination and green chemistries: Activation of dioxygen and in situ hydrogen peroxide generation; bleaching; clay catalysed organic synthesis - Tippu Sheriff

The modeling of small molecule activation in biological systems with current interests in the catalytic activation of dioxygen and the in situ generation of hydrogen peroxide. Applications include low temperature bleaching, selective oxidation, disinfection and the generation of labeled hydrogen peroxide species (e.g. D218O2). These interests involve the synthesis and characterization of novel manganese complexes of biological interest.

Sheriff T.S., Cope S. and Ekwegh M. (2007) Calmagite dye oxidation using in situ generated hydrogen peroxide catalysed by manganese(II) ions, Dalton Transactions, 5119-5122.

Two-component regulatory systems in chloroplasts - John F. Allen

Sujith Puthiyaveetil and John F. Allen have identified a modified histidine sensor kinase in that couples photosynthetic electron transport with transcription of chloroplast DNA. This is further evidence for the prokaryotic nature of bioenergetic organelles of eukaryotic cells. The second component, the response regulator, will be identified, along with the role of this and other two-component systems in redox signalling and the function of cytoplasmic genomes. The project will test the hypothesis that the two-component systems, inherited from the cyanobacterial ancestor of chloroplasts, provide a regulatory coupling between photosynthesis and gene expression.

Adjustable stoichoimetry of membrane-intrinsic complexes in photosynthesis and respirationJohn F. Allen

Chloroplast thylakoids are able to adjust the relative quantities of photosystem I and photosystem II in response to changes in the redox state of the electron carrier, plastoquinone, which connects them. The CoRR hypothesis for the function of chloroplast and mitochondrial genomes predicts that redox control of complex stoichiometry is a general property of all protein subunits encoded in organelle DNA. This prediction will be tested at the protein and functional level, paying particular attention to ATP synthase which is a chimera of nuclear and organelle-encoded subunits, and where the organelle-encoded c-unit of (C)Fo will be quantified relative to nuclear-encoded subunits of (C)F1 under different conditions that are predicted to affect the proton-to-ATP ratio.

Dynamics of macromolecular structures in photosynthetic membranes - Alexander Ruban, John F. Allen, Norbert Krauss

The three-dimensional structures of major membrane-intrinsic complexes of photosynthetic membranes are now known, but there is overwhelming evidence that these each describe only a single form of a complex that switches between alternative structures according to alternative functions, and according to alternative interactions formed with different functional partners. The objective will be to solve the novel structures by X-ray crystallography and electron microscopy in conjunction with advanced spectroscopic techniques. The research will focus particularly on the structural and functional plasticity of chloroplast light-harvesting complex II in its different roles in light-harvesting and energy dissipation, and in its interaction with both photosystem I and photosystem II.

Click” generated bio- and chemo- sensors - Mike Watkinson

We have recently reported on the use of click chemistry to produce a novel Zn sensor agent with exquisite selectivity for zinc over a range of other metals which is able to detect cellular apoptosis (Inorg. Chem., 2009, 48, 319-324). In addition we have developed a new approach to biosensing which relies on the perturbation of a weak metal-ligand interaction through the allosteric binding of a protein to the functionalised ligand (Chem Eur. J., 2009, 15, 3720-3728). We are now seeking to develop this chemistry further in a number of areas and invite applications from interested parties.

The development of C-H oxidation catalysts - Mike Watkinson

We have a long-standing interest in the development of low-temperature bleaching agents for laundry applications and epoxidation (Dalton Trans., 2006, 645-661;Green Chemistry, 2007, 9, 996-1007; J. Mol. Cat. A: Chemical, 2008, 296, 1-8.) and invite applications from interested parties in this area.

Novel C–H functionalization methodologies in organic synthesis - Igor Larrosa

Projects are offered on the development of new C–H arylation methodologies for the synthesis of biaryls, common motives in natural and pharmaceutical products. C–H activation allows for the coupling of two substrates without the need of pre-functionalization, thus following the principles of atom and step economy. This is a highly competitive and high impact area that promises to revolutionize organic synthesis in the near future.

Luminescent metal complexes for optoelectronics based on fluorinated organic ligands - Peter Wyatt

We are preparing new materials designed for use in infrared and visible light emitting devices (e.g. optical amplifiers, light emitting diodes, lasers) with efficient transformation of energy. Metal complexes containing highly fluorinated (or chlorinated) ligands have several advantages over their hydrogen-containing counterparts. The lower vibrational frequency of C–halogen compared with C–H greatly reduces the vibrational quenching of electronically excited lanthanide ions such as Er3+, Nd3+ and Yb3+, thus allowing maximum emission of IR light at useful telecommunications wavelengths, whilst avoiding unwanted heat production1-3. Fluoro-organic materials are often relatively volatile and thermally stable, making them suitable for device fabrication by vacuum deposition. Fluorination of aromatic substances can improve their ability to act as electron transport materials and also promote intersystem crossing, thus allowing greater participation by triplet excited states in the photosensitisation process.
We have reported the sensitisation of near infrared photoluminescence from Er3+ in complexes with the tetrafluoronitrophenoxide ion (1) and from Yb3+ using the pentafluorotropolonate ion (2)4,5. We have also prepared lanthanide complexes of several fluorinated hydroxyketones (3-4), which provide particularly efficient sensitisation of Er3+ and we have described the visible luminescence properties of the new, fully fluorinated, thermally stable zinc complex 5, based on a benzothiazole-containing chromophore6.


 

 

Fully fluorinated complexes with P–O donor groups such as {[(C6F5)2PO]2N}3Er and [(C6F5)2PO2]3Er have a remarkably long-lived IR luminescence, with lifetimes of hundreds of microseconds2,3. However, these systems lack suitable chromophores that can act as photosensitisers for the excitation of erbium ions using low energy (visible light) photons. We therefore propose to modify them to include photosensitisers which may be attached either covalently (e.g. by azide-alkyne ‘click’ chemistry) or non-covalently (by co-sublimation). We shall also examine the effects of introducing high atomic number atoms that promote intersystem crossing.
Promising compounds will be incorporated into organic light emitting diodes and optical amplifiers in association with Professor W. Gillin (School of Physics and Astronomy).

References
1. R. H. C. Tan, M. Motevalli, I. Abrahams, P. B. Wyatt and W. P. Gillin, J. Phys. Chem. B, 2006, 110, 24476-24479.  
2. G. Mancino, A. J. Ferguson, A. Beeby, N. J. Long and T. S. Jones, J. Am. Chem. Soc. 2005, 127, 524-525.
3. Y. Zheng, J. Pearson, R. H. C. Tan, W. P. Gillin and P. B. Wyatt, Journal of Materials Science: Materials in Electronics, 2009, 20, S430-S434.
4. Y. Zheng, M. Motevalli,  R. H. C. Tan, I. Abrahams, W. P. Gillin and P. B. Wyatt, Polyhedron, 2008, 27, 1503-1510.
5. I. Hernández, Y.-X. Zheng, M. Motevalli, R. H. Tan, W. P. Gillin and P. B. Wyatt, Chem. Commun., 2013, 1933-1935.
6. Z. Li,  A. Dellali, J.  Malik,  M. Motevalli,  R. M. Nix, T. Olukoya, Y. Peng, H. Ye, W. P. Gillin,  I. Hernández,  and P. B. Wyatt, Inorg. Chem., 2013, 52, 1379-1387.

 

Chemical synthesis and structural characterization of peptides derived by oxidative modification of L-histidine - Peter Wyatt

Histidine is well known to bind biologically relevant, redox-active transition metal ions such as Cu2+. Several pathways for oxidative modification of histidine in peptides under physiological conditions have been suggested (e.g. by oxidation to ‘oxohistidine’ or by electrophilic attack of lipid peroxidation products at the imidazole nitrogen).1 The oxidation products are usually not well characterized in chemical terms and not readily accessible in preparatively useful amounts. The aims of this project are (i) to establish efficient routes for the preparation of these histidine derivatives, (ii) to develop protecting group strategies for incorporating them into standard (Fmoc) methodology for peptide synthesis and to determine the structural consequences of their presence in biologically relevant peptides such as the amyloid beta peptide of Alzheimer’s disease.

For a review, see K. Uchida, Amino Acids, 2003, 25, 249-257

Exploiting the cytochrome P450 system to develop drugs targeting trypanosomes - Shane Wilkinson

Across the tropics over 10 million people are infected by the protozoan parasites Trypanosoma brucei and Trypanosoma cruzi. With no prospect of a vaccine, drugs are the only viable option to treat these pathogens. However, as many agents currently used to treat these pathogens have associated problems there is an urgent need for new, cheap, less toxic therapies.
In many eukaryotic organisms the cytochrome P450 (CYP) system plays a key role a number of diverse pathways and has been implicated in the activation of a number of prodrugs including the oxazaphosphorine class of anticancer compounds. Moreover, recent work has proposed that the CYP system may play a role in mediating drug resistance to nitroheterocyclic compounds, agents used to treat trypanosomal infections. We have now identified several components of CYP pathway from the trypanosomal genome databases. The aims of this project are to: 1) determine the biochemical properties of the trypanosomal CYP network, 2) establish the role of these systems in trypanosomes and 3) exploit such activities in the search for novel trypanocidal therapies. A link between nitroheterocyclic drug resistance in trypanosomes and the CYP system will also be explored.

The project will exploit current biochemical, molecular genetics and parasitiology expertise at QMUL. Instruction in GMP will be given, with emphasis on culturing & genetic manipulation of category 2 & 3 pathogens. The successful candidate will be encouraged to publish and present their results at international conferences as well as attend appropriate courses for their career development.

References:

  1. Wilkinson, S. R., M. C. Taylor, D. Horn, J. M. Kelly and I. Cheeseman (2008) A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc. Natl. Acad. Sci. 105, 5022-5027.
  2. Taylor, M. C., H. Kaur, B. Blessington, J. M. Kelly and S. R. Wilkinson. (2008) Validation of spermidine synthase as a drug target in African trypanosomes. Biochem. J. 409, 563-569.
  3. Wilkinson, S.R., S.R. Prathalingam, A. Ahmed, D. Horn and J.M. Kelly. (2006) Functional characterisation of the iron superoxide dismutase gene repertoire in Trypanosoma brucei. Free Radic Biol Med. 40, 198-209.
  4. Wilkinson, S.R., S.R. Prathalingam D. Horn and J.M. Kelly. (2005) Vitamin C biosynthesis in trypanosomes; a new role for the glycosome Proc. Natl. Acad. Sci. 102, 11645-11650.
  5. Wilkinson, S.R., D. Horn, R. Pathalingam and J.M. Kelly. (2003) RNAi identifies two hydroperoxide metabolising enzymes that are essential to the bloodstream form of the African trypanosome. Journal of Biological Chemistry 278, 31640-31646.

The neurobiological basis of drug dependence - Caroline Brennan

Addiction is a psychiatric disorder with a huge social and financial cost. While there have been key advances in understanding of the underlying neurocircuitry and adaptation (Kelley, 2004), far less is known of developmental and genetic factors that contribute to vulnerability to addiction. Maternal smoking and exposure to cigarette smoke during childhood and adolescence is known to lead to an increased vulnerability to drug dependence in later life (Button et al., 2007). Several components of smoke including nitric oxide and monoaminoxidase inhibitors may contribute to this increased vulnerability. However, recent studies have shown that prenatal exposure to nicotine, the primary reinforcing agent in tobacco smoke, leads to altered sensitivity to subsequent nicotine exposure (or other drugs of abuse), that may increase vulnerability to dependence in later life (Dwyer et al., 2008; Franke et al., 2007; Franke et al., 2008; Levin et al., 2006a; Pauly and Slotkin, 2008; Slotkin et al., 2008). (A similar situation is seen in off-spring pre-natally exposure to other drugs of abuse.) Despite significant advances, the molecular mechanisms by which this occurs and genetic factors that regulate nicotine-induced vulnerability to dependence are not fully understood. Advances in understanding that have been made to date have relied heavily on hypothesis driven and candidate gene approaches. Mutagenesis screens, as commonly used in zebrafish, offer the advantage of not needing to know the genes or pathways involved in advance, thus they may lead to novel and unexpected breakthroughs (e.g.(Crosier et al., 2002; Ettl et al., 2006; Jagadeeswaran et al., 2000)). Our research aims use zebrafish to further understanding of the factors underlying vulnerability to drug dependence. One key approach is to develop and perform mutagenesis screens in zebrafish to identify factors influencing development of the ‘reward’ pathway and behavioural responses to drugs of abuse.

Projects investigating the neurobiological basis of vulnerability to drug dependence using zebrafish as a model system are encouraged. 

Social learning across species boundaries - Lars Chittka

The study of social learning - how animals obtain information not by individual exploration of the environment, but instead by extracting information from other animals - has almost entirely focussed on information transmission within species boundaries. This raises the question on whether animals do, or should, predominantly copy from conspecifics. While genetic information, by definition, might be transmitted only within species, social information might transcend species boundaries freely. Some animals might be relatively flexible in what other animals they copy, and subsequently evaluate the usefulness of the copied behaviour, or the usefulness of the particular model in general. In fact, where resources as shared (e.g. flowers between generalist pollinators) or where generalist predators lurk (e.g. crocodiles in a river), picking up information from heterospecifics may be just as valuable as from members of the same species. This raises the question of whether conspecifics are indeed a unique entity in social learning, or whether animals might simply learn to pick any environmental cue that facilitates identifying salient conditions in the environment. In this project, we will study these questions using bumblebee pollinators.

Structural basis of phytochromes -photoreceptor function - Norbert Krauss

Phytochromes are photoreceptors in plants, bacteria and fungi which bind linear tetrapyrroles (bilins) as chromophores and are most sensitive in the red and far-red region of the visible spectrum. In bacteria, phytochromes consist of a photosensory domain and a signal-output histidine kinase domain which is related to those found in bacterial two-component systems. The photochemical key event in phytochromes upon absorption of light is a switch between two stable, spectrally distinct forms (Pr and Pfr) by isomerisation of a double bond which is part of the linkage between pyrrole rings C and D. The activity of the histidine kinase domain is modulated by the light-dependent state of the photosensory domain. The objective of this project is to determine the structures of a bacterial phytochrome by X-ray crystallography in both the Pr and the Pfr states in order to resolve the molecular mechanisms of photoconversion and modulation of the histidine kinase activity.

Plant cytogenetics and genome evolution - Andrew Leitch

Places are available to active research scientists who are interested in the evolution of plant genomes, in particular the evolution of chromosome and karyotype structure including studies into the origin, divergence and distribution, of repetitive sequences. We have particular expertise and skills in plant polyploidy and telomere biology and would welcome scientists interested in these and related areas. This work extends into agricultural sciences, in particular the development of wheat and non-food crops, especially those crops used for biofuels.

Comparative physiology and evolution of neuropeptide signalling - Maurice Elphick

Neuropeptides and peptide hormones have fundamental roles in controlling, regulating and integrating physiological and behavioural processes in humans and other animals. I am interested in reconstructing the evolutionary history of neuropeptide signalling systems and investigating how neuropeptides are utilised to co-ordinate physiological processes and behaviour in animals.
The primary focus of my neuropeptide research is on echinoderms (starfish, sea urchins, sea cucumbers), which are of special interest for a number of reasons. Firstly, as deuterostomes, echinoderms are much more closely related to vertebrates than the majority of invertebrates, and therefore research on echinoderms can shed light on the evolutionary origins of vertebrate characters. Secondly, echinoderms have many remarkable morphological and physiological characteristics – they are typically five-sided and have a unique ability to rapidly change (under neural control) the stiffness of body wall collagenous tissue; they also have amazing powers of regeneration, which makes them of great interest from a medical perspective. Thirdly, echinoderms are of economic importance both as predators on shellfish (starfish) and as foodstuffs (sea urchins, sea cucumbers).
I pioneered research on neuropeptides in echinoderms with the discovery of the SALMFamide neuropeptide family (Elphick et al., 1991). Now over twenty years later we are entering a new era for research on neuropeptide systems in echinoderms. Sequencing of the genomes/transcriptomes of several echinoderm species is providing fascinating new insights on the evolution and diversity of neuropeptide systems (Rowe and Elphick, 2012; Elphick, 2012; Elphick et al., 2013). Moreover, with the falling cost of DNA sequencing, any echinoderm species is now accessible to transcriptomic analysis of neuropeptide systems. For the first time we can comprehensively investigate neuropeptide function in animals that hitherto were intractable for molecular physiological studies. Utilising recently obtained neural transcriptome data, my lab is using the common starfish Asterias rubens as a model system to investigate the evolution and physiological roles of neuropeptide systems.
I welcome researchers that share my interest in the comparative physiology and evolution of neuropeptide signalling systems to contact me. I am keen to host postgraduate and postdoctoral researchers in my lab at Queen Mary University of London and to collaborate with other scientists interested in this area of research.

Publications: For further details of the recent publications from the Elphick lab see:
http://www.researchpublications.qmul.ac.uk/publications/staff/21463.html

Structural molecular biology of enzymes and bacterial secretion systems - Richard Pickersgill

We are studying the structure and function of a number of important molecular machines using molecular biology, X-ray crystallography and NMR spectroscopy. The first of these, the type II secretion system delivers potent toxins causing disease in man. We recently solved the structure of a protein domain important for the assembly of this bacterial secretion system and aim to explore the architecture further and elucidate its mechanism. In a second project area, we have established the mode of action of a key Shigella effector, a bacterium that kills millions of people each year; we aim to study the structure and function of additional Shigella protein effectors. The remaining two project areas are cobalamin (vitamin B12) biosynthesis and bacterial microcompartments. Cobalamin is the most complex small molecule in biology requiring 30 biosynthetic steps to construct. It is the only contracted tetrapyrrole in nature and the only molecule that exploits the chemistry of the Co-C bond. We recently solved the structure of the ring-contraction enzyme and are working to understand how it works and how these enzymes discriminate between closely related intermediates. Bacterial microcompartments form icosahedral shell structures that sequester a specific biosynthetic pathway and intermediates; they offer exciting opportunities in synthetic biology.

Evolutionary changes in arthropod neurogenesis - Angelika Stollewerk

My lab is interested in the question of how neural development has been modified during evolution to give rise to the high diversity of adult central and sensory nervous systems in arthropods. Evolutionary modifications of neural networks can in principle be achieved during different processes of neural development: (1) by changes in generation of neural precursors (early neurogenesis) (2) changes in establishment of neural precursor identity and (3) modifications of axonal pathfinding. We are analysing all 3 processes in representatives of each of the four euarthropod groups including model organisms (Drosophila melanogaster, Tribolium castaneum, Daphnia magna) by applying morphological and molecular techniques. Applicants can choose a suitable project within this framework according to agreement. 

Nanoparticles for applications as enzyme mimics and drug delivery - Marina Resmini

The main research interests of our group are at the interface between chemistry and biology, in the broad area of biomimetic systems, in particular artificial receptors and catalysts. Work has focused on the synthesis and characterisation of novel enzyme-like catalysts, first via the catalytic antibody approach and more recently with molecular imprinted polymers. Molecular imprinting is a synthetic approach for the generation of recognition sites in a macromolecular matrix using a molecular template and functional monomers in a casting procedure. Our group has developed a new approach by synthesising a small library of polymerisable aminoacids to use as functional monomers and by applying, for the first time, the imprinting technology to micro- and nano-gels for the synthesis of novel catalysts. The expertise acquired in this field is now being applied to the synthesis and development of nanomaterials for applications as catalysts, sensors and nanovectors for drug delivery. Projects for fellowship applications are available in this area of interest. Further information can be obtained from the website and by contacting Dr. Resmini via email.

Methane-subsidised production in fast flowing rivers: a novel mechanism of carbon and energy flux - Mark Trimmer and Jonathan Grey

As biologists (and chemists), we are probably all familiar with the basic principle that life on earth is reliant on primary production driven by the sun. There was a great deal of interest in 1977 when images of bizarre 6ft tubeworms and giant clams came up from the depths of the Pacific to reveal significant production, indeed whole chemosynthetic ecosystems, coupled to the oxidation of sulphur belching forth from ‘black smokers’ but few, if any, would suspect that a chemosynthetic mode of life may be significant in the classic chalk rivers of southern England. However, a fortuitous finding, as part of a wider NERC LOCAR project into the ecological significance of river water and groundwater exchange (Pretty, Hildrew & Trimmer 2006), suggests that this may actually be the case. We measured the d13C values of common aquatic invertebrates and their putative food sources in the river Lambourn and, whereas the d13C for invertebrates such as Gammarus and Simulium reflected that of the dominant primary production (i.e. fractionated to the right), the cased larvae of the caddisflies Agapetus, Silo and Drusus were consistently isotopically light. Remarkably, such low d13C values characterise chemosynthesis coupled to methane oxidation and our calculations suggest that the caddisflies are receiving a 20 to 25 % carbon ‘subsidy’ via this route (Trimmer et al in press).

We (Trimmer & Grey) are keen to pursue this novel and exciting research via a motivated and talented post-doctoral researcher with interests in aquatic biogeochemistry and stable isotope ecology via the Marie Curie fellowship scheme. Applicants with a proven track record (e.g. relevant publications) should contact either supervisor in the first instance.

J.L. Pretty, A.G. Hildrew, M. Trimmer (2006) Nutrient dynamics in relation to surface–subsurface hydrological exchange in a groundwater fed chalk stream. Journal of Hydrology 330, 84– 100.

Novel phosphate based glasses as biomaterials for dentistry - Isaac Abrahams

Phosphate based compounds have long been investigated as potential biomedical materials, in particular calcium phosphates, because of their close chemical relationship with natural bone. When used as replacement materials for bone or as dental cements there is often a requirement for subsequent X-ray examination of the material. In this case it is an advantage to have a system with high radio-opacity. In the case of biomedically relevant calcium phosphate glasses, this can be achieved by substitution of Ca2+ by heavier ions such as Sr2+ or Y3+. The proposed project involves the development and characterization of phosphate based glasses and glass ceramics for use as biomedical materials in dentistry and maxillo-facial surgery. Using glass based compositions it is possible to tailor properties such as mechanical strength, solubility and bioactivity. The project will be carried out in collaboration with the Biomaterials Department at the Eastman Dental Institute, University College London.

New oxide ion conductors for fuel cell and sensor applications
- Isaac Abrahams

Oxide ion conducting solid electrolytes are the subject of considerable interest due to their potential applications in solid oxide fuel cells, gas sensors and gas separation membranes. A central aim of this research is to identify new compounds that show high oxide-ion conductivities at intermediate temperatures. The project seeks develop new fast oxide ion conductors based to be used in the intermediate temperature range. The work will involve structural and electrical characterisation and involve the latest total neutron scattering methods.

Protein misfolding and amyloid fibril assembly in Alzheimer’s and Mad Cow disease - John Viles

The project will involve a number of spectroscopic and biophysical techniques to investigate how metal ions influence the structure and fibrillisation of amyloid-beta peptide in Alzheimer’s disease and the prion protein in mad-cow disease. In particular, NMR, CD and EPR for which my lab has proven experience. You will also gain understanding of amyloid formation, protein folding, as well as binding affinities, protein expression and co-ordination chemistry. You will require a degree of computer literacy. These techniques will equip you with the skills necessary to be an effective researcher in structural biology.
Alzheimer’s disease (AD) is characterised by deposits of amyloid plaques. Fibrils of amyloid-beta peptide are the main constituent of these plaques. It is yet to be established what triggers amyloid formation in vivo, although metal ions, amyloid-beta peptide chemical modification, amyloid-beta peptide mutation, ionic strength and pH have all been shown to influence this process. This proposal will investigate factors that effect the formation and structure of amyloid-beta fibrils.
The prion protein (PrP) is a copper binding cell surface glyco-protein. Misfolding of PrP into a beta-sheet rich conformation is responsible for neurodegenerative diseases such as CJD in humans and BSE (mad-cow disease) in cattle. You will study the structure and folding of the prion protein and the direct binding of amyloid-beta oligomers to the cellular form of the prion protein PrPC.
Send a CV and the names and contact details of two academic referees to: Dr John H Viles. For further detail of research in my lab and a list of publications go to my website.

Marine and estuarine ecology - Rob Hughes

My research predominantly concerns the ecology and conservation of estuarine habitats of economic and conservation importance, particularly saltmarshes and mudflats which are declining. Research questions relate to fundamental processes and how these can relate to management for conservation purposes, particularly in the face of predicted increased rates of sea level rise.

These include:
1. How do saltmarshes develop and how is this related to rising sea level?  What determines the pattern of creek development?
2. What is the interaction of the biological processes (e.g. bioturbation by deposit feeders) and physical environment in the erosion of saltmarshes, including the internal creeks.
3. What is the effect of reclaiming saltmarsh areas, by building sea walls, on the remaining saltmarshes?   Are these further eroded or stabilised?
4. What determines the elevation (with respect to sea level) of saltmarshes and mudflats?  Are they related and do they change?
5. What are the effects of nutrient enrichment/pollution on the stability of intertidal sediments? Does enrichment of the estuaries increase benthic productivity and increase the rates of bioturbation and erosion?

Understanding social behaviour – a genomic approach - Chris Faulkes

Using African mole-rats as a model system we aim to characterise genes implicated in the expression of social and mating behaviours, in particular, receptors for the two hormones oxytocin and vasopressin.  Studies on North American voles have shown that differences in the patterns of expression for these receptors in the forebrain underpin species-typical patterns of behaviour (e.g. monogamous versus promiscuous mating systems). These differences in expression are associated with differences in the promoter regions of the receptor genes, suggesting that a strong genetic component exists for these complex mammalian behaviours. Such findings may contribute to our understanding of certain human behaviours. For example, oxytocin, dubbed by some as “the love molecule”, has been shown to increase interpersonal trust, the memory of familiar faces; furthermore, differences in the oxytocin receptor gene have been associated with autism spectrum disorders. Our own recent studies suggest a broad role for oxytocin in facilitating social and cooperative behaviours1. Utilizing our unique access to a variety of mole-rat species and our recently constructed genomic libraries, we now aim to screen for and then sequence specific genes of interest. Using comparative analyses we will elucidate genetic differences among species marked by different levels of social and affiliative behaviour.
 
1Kalamatianos T., Faulkes, C.G, Oosthuizen, M.K., Bennett, N.C & Coen, C.W. (2010) Telencephalic binding sites for oxytocin reflect social organisation: evidence from eusocial naked mole-rats and solitary Cape mole-rats. Journal of Comparative Neurology. 518, 1792-1813.

Automated analyses of full behavioural repertoires by motion capture and clustering algorithms - Lars Chittka

Social insects often have astonishingly rich behavioural repertoires. In a meta-analysis of behavioural repertoires across animal species, the number of recognisable, stereotyped behaviour routines in many insects was on a par with some mammals: moose were listed with 22 recognisable behaviours, De Brazza’s monkeys 44, and 4 year old humans 111 behaviours; honeybees had 59. The number of skeletal muscles in insects rivals and indeed exceeds that of some mammals – thus, while the morphological toolkit to generate behavioural diversity is miniaturised in insects compared to mammals, it is not necessarily less complex. The quantification of behaviour types across animals is undoubtedly useful. However, a complication is that the classification of behaviour typically follows entirely subjective criteria and is therefore difficult to compare across animals: for example ‘leg extension’, ‘bee waggle dance’ and ‘consensus building in bee swarms’ are not equivalent behavioural classifications, and are to some extent nested within one another. It is therefore necessary to classify behaviour by automated procedures so that they can be objectively measured and compared using an ‘ethomics’ approach, since our plan here is to identify the minimum neural circuitry that might mediate all behavioural routines in bumblebees and honeybees. We will use 3D video analysis, and automated motion capture procedures at several spatial scales, from minute movements of legs, antennae and heads to intermediate scale movement patterns such as the honeybee dance, to spatial movement patterns while foraging outside the hive. Similar techniques have recently been tested on head movements of blowflies during cruising flight but there has been no attempt so far to dissect and classify an entire behavioural repertoire in an animal using such methods, and the plan here is to do just that.

Large-scale automated analytical tools will be developed to mine effectively the data collected with the aim of finding prototypical and atypical behaviours. To this end we will extract motion patterns from recorded dynamic scenes by analysing the patterns of a large number of moving bees and by quantifying the variability of the behaviour of individual bees. To discover prototypical activity models we will implement procedures for clustering accumulated trajectory data into representative patterns. To encode the variability of the behavioural repertoires we will develop a dedicated alphabet and syntax of movements that can be effectively compared between individuals and species. The comparison between honeybees and bumblebees will be especially informative here, since only the former have the renowned dance communication systems and complex consensus building processes in swarming. Our automated ‘data mining’ approach will also facilitate the discovery of new behaviours that have so far escaped the attention of human observers.

Artificial neuronal networks for multi-tasking in bee cognition and behaviour - Lars Chittka

Artificial neural network analyses typically show that the minimum number of neurons necessary to perform a variety of cognitive tasks is exceedingly small. For example, a simple visual pattern categorisation task can be solved with a network consisting of 7 sensory neurons and 5 interneurons, and selective attention could be generated with 9 sensory neurons and less than a dozen interneurons. Similarly simple networks can be used for sequence learning, as used for example in landmark navigation by bees, and path integration. Thus, several of the behavioural/cognitive feats now demonstrated in insects can, in principle, be solved with neuronal networks that consist of dozens or hundreds, not millions, of neurons. However, many of these network models are neither closely inspired by neurobiological data, nor are they designed to solve more than a single task. Here we plan to develop artificial neural networks that mimic the capacity of an entire bee nervous system, both in terms of the repertoire of hard-wired, behavioural routines as well as generating the full range of cognitive abilities in bees.

There is a wealth of information that could be gleaned from such ‘brain-wide’ (and indeed nervous system wide) modelling for an insect. Attempts to model the mammalian brain, such as the Blue Brain Project face extraordinary challenges because such models will ultimately have to incorporate many billions of neurons (and their connections) whereas the number in bees is under a million. The beauty of studying a miniature nervous system (that nonetheless generates a rich behaviour repertoire) is that it will allow us to pinpoint what circuitry is minimally needed to mimic the wide range of behavioural competencies (including foraging, navigation, learning) and their successful interaction in integrated behaviour over extended time periods. How extensive does the circuitry have to be in order to generate the range of known behavioural output? How does this compare to real brains? What is gained with higher neuron numbers/larger brains? What are the optimal solutions if we place constraints on a range of neuroanatomical parameters e.g. total neuron number, number of synapses, and architecture topology? How specialised do circuits have to be, and what extent of modularity is useful? How much neuronal re-use (of individual neurons or circuits) can be tolerated without substantial interference between different behavioural requirements? How much extra circuitry is needed to generate a honeybee’s ‘waggle dance’ from the pattern generator for basic forward walking? How much behaviour/cognitive diversity can emerge from replicating identical circuits multiple times? What mechanisms are needed for behaviour integration and smooth transitions between behaviour routines where needed? We will devise and test neural circuits grounded in current knowledge of neuroanatomy and neurophysiology. A modular approach will be used, in which a high-level brain architecture description is gradually elaborated. We will experiment with simple Hebbian learning, as well as Izhikevich’s learning rule, to explore what complex emergent phenomena might be generated using relatively simple mechanisms at the local (synapse) level and known local circuit architecture. We will develop evolving artificial neural networks, with each stage inheriting knowledge from the previous one to enhance simulation efficacy and performance. Results will allow us to predict the minimum number of evolutionary changes needed to generate novel behavioural competencies. We will gain invaluable information about how cognition could be mediated in neuronal circuit terms, and we will verify these predictions by multi-electrode recordings from the bee brain. Models will also allow crisp predictions of emergent behavioural limitations implicit in certain circuits that can be tested directly in the laboratory.  

Multi-electrode recordings from the bee brains to explore the neuronal ensemble code for visual cognitive tasks - Lars Chittka

Fundamental progress has already been achieved in understanding which brain areas in insects are responsible for which tasks, but to understand the circuits that might underpin higher cognitive function, it will be necessary to record the temporal activities of multiple individual nerve cells simultaneously. So far, the electrophysiological study of bee visual cognition has been hampered by the fact that visual learning is severely impeded in tethered bees. However, there might be a simple explanation: if visual perception depends on active visual probing of the environment by means of self-generated movement, then tethered bees (which cannot move their heads to scan visual patterns) are constrained to fail in any but the most simple discrimination tasks. This view is in line with an ecological (Gibsonian) perspective on perception and cognition, meaning that these can only be understood in an embodied, ecological context. Our strategy will be to ‘re-embody’ a restrained bee using a virtual reality visual simulator. The essence of the strategy will be to record the bee’s self-generated motor output and use it to control the visual simulation in predictable ways. The sensorimotor loop will thus remain closed, which we hypothesize to be essential for any complex form of visual learning.
If a particular motor pattern has an influence on visual feedback then it can be employed in the control of behaviour. Our initial experiments will involve tethered flight in front of a computer generated visual display, where the bee will be trained to centre on a target stimulus on the screen. Visual stimulation will be under the bees own control: we will record electromyographically from direct flight muscles and use the output to control visual stimulus position. In subsequent experiments we will explore the use of novel sensorimotor contingencies, for example using leg movements to control lateral image displacement. Our objective is to record dynamic correlations between multiple visual and motor areas, where the salience of the visual stimulus is partly decided by the bee. Initially, we will use twisted wire electrodes in the mushroom bodies, for recording both field potentials and single unit activity. A variety of designs will be tested subsequently in optic lobe, including conventional polytrodes, and newer, evolving technologies (e.g., carbon fibre). We will use simultaneous multi-unit extracellular recording with single electrode intracellular recording to correlate field potentials with synaptic activity. This will inform the analysis of field potentials recorded in minimally restrained bees. This work will be performed in collaboration with Peter Skorupski, a skilled electrophysiologist at Queen Mary University of London.

Bioinformatics for genomics of emerging model organisms - Yannick Wurm

The 10,000-fold drop in the cost of DNA sequencing over the past five years means that any lab can sequence anything - and lots of it. This brings exciting new opportunities but also new challenges. We develop innovative tools and approaches to facilitate the work of biologists dealing with large volumes of data from emerging model organisms. For this we identify problems they face, and address them while trying to consider how Apple/Google/Facebook would do it. For example:

* BLAST is the most commonly used bioinformatics tool in biology. But the graphical interface is clunky at best, and setting it up for private data is a nightmare. Thus we're developing [SequenceServer][http://www.sequenceserver.com], which aims to make both aspects easily accessible.
* Sequencing genomes has become straightforward. But gene prediction approaches still have much potential. Thus individual gene models must be manually curated by biologists before rigorous analyses can be performed. Unfortunately this can take hours for a single gene -  making many multi-species multi-gene analyses impossible. We are thus developping an infrastructure that aims to "crowd-source" gene model curation tasks to members of the general public.

The needs for facilitating biological research continue to grow & additional ideas are in store. We are particularly interested in collaborating with individuals that have interdisciplinary experience with modern biological data, software development, and/or web app development.

Structural study of new compounds in the treatment of Alzheimer’s disease - Ali Zarbakhsh

Alzheimer’s disease (AD), the most common form of dementia, is a devastating neurodegenerative disorder and is the fourth most common cause of death in the World.  AD presents challenges in an ageing population.
Structural studies proposed will provide the vital information about the interaction/conformation of organophosphonate compound with structure of lipid in the presence/absence of the A (1-42) peptides. These new lead compounds have been developed at QM for the treatment of Alzheimer’s disease.   Their design is based on phosphonate substituted bioactive organic cores, where the role of the phosphonate group is to facilitate ionophore activity. They have shown promising performance in a battery of tests including Abeta amyloid toxicity, AMES test (lack of genotoxicity), rat plasma, human and mouse liver microsomal stability as well as displaying beneficial neurotrophic effects in primary neurons. This project will provide the fundamental information needed to understand the full interaction mechanism leading to optimisation of the molecular design.
This project will develop in parallel the techniques of Neutron  reflectometery (NR) (ISIS, Oxfordshire, UK & ILL, Grenoble France), X-ray reflectometery (XR) (Diamond Light source, Oxfordshire, UK), tapping mode AFM and Brewster Angle microscopy (BAM) to resolve the structure of both biological and non-biological membranes at air-liquid and, more importantly, liquid-liquid interfaces.  The appropriate sensitivity (Å length scale) of NR is well suited to resolving the structure of lamellar system and will be the principle technique in this work in addition to information on binding mechanism. Complementary XR will also be explored to provide additional data on molecular structure at these interfaces.

Evolutionary genetics and genomics of mammals - Stephen Rossiter

I invite enquiries from potential Marie Curie fellows with strong CVs and expertise in evolutionary genetics and genomics. The lab has a strong background in bat genetics although we are also interested in other groups. Projects could potentially focus on any aspects of adaptation, population divergence and speciation in mammals.

1. Genetic basis of adaptive radiations. Existing projects are combining high throughput sequencing techniques (genomic, RNAseq, targeted sequence capture) with bioinformatics pipeline development to screen large numbers of loci in hyper-diverse clades of bats, rodents and other taxa.

2. Genome-wide scans of loci underpinning population divergence and incipient ecological speciation.

3. Quantitative genetics of traits in wild bat populations using genomic approaches (SNP analyses, RADseq) for parentage inference and pedigree reconstruction.

Evolutionary genomics of insect societies - Yannick Wurm

Extensive theoretical work has explained how and why complex societies evolve. However, only little is known about the genes and evolutionary mechanisms responsible for social phenotypes. We have been identifying genes and mechanisms involved in the evolution of insect societies using modern genomics tools (Illumina, RNAseq, RADseq...). For example we recently sequenced and analyzed the genome of the invasive red fire ant Solenopsis invicta (PNAS 2011) and determined that a fundamental social trait in this species is determined by variants of a social chromosome (Nature 2013).

Building upon on such work we are interested in themes including the genetics of behavior, the interplay between social evolution and genome evolution, and the molecular mechanisms responsible for differences between castes.

Invitations are invited from candidates with experience in population genomics, molecular evolution, or the genetics of model organisms (C. elegans, Drosophila), as well as from social insect researchers interested in applying modern approaches to outstanding questions.

Relevant publications:
Wang and Wurm et al (2013) A Y-like social chromosome causes alternative colony organization in fire ants. Nature.
Wurm et al (2011) The genome of the fire ant Solenopsis invicta. PNAS.
Gadau et al (2012) The genomic impact of 100 million years of social evolution in seven ant species. Trends in Genetics.
Hunt et al (2011) Relaxed selection is a precursor to the evolution of phenotypic plasticity. PNAS
Nygaard et al (2011) The genome of the leaf-cutting ant Acromyrmex echinatior suggests key adaptations to advanced social life and fungus farming. Genome Research.
Wurm et al (2010) Changes in reproductive roles are associated with changes in gene expression in fire ant queens. Molecular Ecology.

Understanding the 'genomic action potential' - David Clayton

(see: Clayton 2000; Clayton 2013 (in press)). Brain activity involves not only acute changes in electrophysiological signaling (e.g., the classic 'action potential') but also acute changes in gene expression. It is hypothesized that such 'genomic action potentials' integrate and process information but over a much longer timecourse than do the more familiar electrophysiological action potentials. Tests of this will involve analysis of how genomic responses to experience vary with developmental stage, social interactions and stimulus salience – factors that can be readily manipulated using the zebra finch as a model.

Computational resources for neurogenomics - David Clayton

(see: Replogle 2008; Drnevich 2012).  Genomic sequencing technologies are changing biological science, and we continue to develop efficient strategies for applying these technologies in research using songbirds. Opportunities exist for refining servers, databases, tools and pipelines to support RNAseq analysis of complex changes in gene expression. Opportunities also exist for comparative transcriptomics of songbird species (in collaboration with Chris Balakrishnan).

Analysing social behaviour in the domesticated zebra finch - David Clayton

(with Sarah London and Saurabh Sinha). We breed and maintain domesticated zebra finches in naturalistic indoor aviaries, where the birds can be readily observed. We have accumulated a large volume quantitative data on social interactions in this context, and opportunities exist for developing statistical and computational analyses of these and future data sets.

Non-invasive imaging of neurogenomic function - David Clayton

With several collaborators we continue to explore nIRS, fMRI and other non-invasive imaging techniques to probe how changes in gene expression relate to changes in brain activity.

Targeted molecular manipulation of genes implicated in neural plasticity - David Clayton

(e.g., microRNAs, neuropeptides, immune genes, NR4A3, estrogen). Our recent studies (both published and unpublished) have demonstrated changes in expression of many different genes during juvenile song learning and adult song perception. Opportunities exist to test hypotheses about the functions of these various changes.

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