Structural studies to advance understanding of IgM and its complement and receptor interactions

Lead Research Organisation: King's College London
Department Name: Randall Div of Cell and Molecular Biophy

Abstract

The human immune system provides protection against foreign organisms including bacteria, viruses and parasites through various cells such as the white blood cells, and proteins such as antibodies. In man, as in other animals, there are specialized types of antibody, but the type known as IgM is the most evolutionarily conserved and is present in all vertebrates that have antibodies. Not surprisingly, it performs essential functions in immunity, but in fact is present in the blood even before an individual encounters an invading organism or foreign "antigen", thus providing general protection against common pathogens. This circulating IgM also plays a role assisting in the clearance of dead and dying cells, an essential and continuous activity; when it fails, the build up of these cells and their contents can cause dangerous conditions and can lead to autoimmune reactions, in which the immune system turns against the individual's own proteins. IgM also determines the course of a healthy immune response, and once it has recognized an antigen as foreign, it binds and then activates defence mechanisms that will eventually lead to the clearance of the antigen. The initiation of these mechanisms involves interactions with other protein molecules in the blood, one of which is called C1q, or on the surfaces of various cells - these latter molecules are called "receptors" for IgM. One of these receptors was only identified three years ago and appears to enhance the immune response, while another that we will study may play an inhibitory role. Positive and negative feedback in the regulation of an immune respose is critical for health: over-reaction (allergic hypersensitivity for example, although caused by another type of antibody, or an auto-immune reaction initiated by IgM) is just as dangerous as under-reaction. Very little is known about any of these interactions and virtually nothing about the way in which they activate the defence mechanisms; the aim of this project is to advance our understanding of these key steps in the immune response through studying the structures of these molecules.

One remarkable aspect of the structure of the IgM molecule is that it is "polymeric", and much larger than the other types of antibody. Most antibodies are Y-shaped, with two "arms" to detect and bind to antigens, and a "stem" through which they bind to other molecules and to receptors on cells. IgM consists of either five or six of these Y-shaped units linked closely together in a ring. Yet despite their large size, ubiquitous occurrence and fundamental importance to human health, we have no detailed knowledge of the structure of IgM. We don't know how the units fit together, and such knowledge is essential if we are to understand how IgM works: how for example does it prevent binding to C1q until it senses a foreign antigen? Sometimes we would like to control the activities of IgM, such as when it is administered for therapeutic purposes and we want to restrict its ability to activate inflammatory reactions; we will only be able to do this if we know how IgM works and how it binds to C1q and to its receptors.

The work will involve producing the key parts of the IgM molecule, both as the single "monomeric" pieces and as the pentamer and hexamer. These have never been made before in a pure enough form to study their structure. We shall also produce the IgM-binding parts of the C1q and IgM receptor proteins. To determine the detailed three-dimensional structures of these molecules and to see how they interact with each other, we shall employ a technique that involves X-rays to locate the positions of all of the atoms in the structure. With other techniques we will measure the strengths of the binding interactions and understand how we might control them. These studies will thus reveal fundamental mechanisms of immunity and will have longer-term benefits for engineering the activities of IgM when used therapeutically.

Technical Summary

IgM is the antibody of the primary immune response, but it also provides protection even before antigen is encountered, and controls the secondary response and the development of autoimmunity, among other roles. Nothing is known in detail about its polymeric structure, nor how this controls its complement-activating and receptor-binding activities. Monomeric IgM also forms part of the B cell receptor for antigen. We shall express, crystallize and carry out binding studies on a range of molecular species in order to provide a sound basis for understanding, and in future engineering, the functional biology of IgM. We shall express IgM-Fc including the Cm2 domains, and without them as Fcm3-4, including various glycoforms both with and without the tailpiece, and also express recombinant pentameric and hexameric IgM-Fc, with and without J-chain respectively. The globular head domain of the first sub-component of complement, gC1q, will be expressed, as well as the IgM-binding Ig-like domains of Fca/mR and FcmR, the two immuno-modulatory Fc receptors. Crystallization and structure determination will be the goal for each of these molecules and their complexes, together with binding studies by surface plasmon resonance (Biacore) and fluorescence anisotropy to determine affinities and mutual compatibility of these interactions, with ITC and/or AUC to determine stoichiometries as appropriate. Ion mobility MS and FRET labeling will be used to determine the shape and flexibility of IgM-Fc, in particular to establish whether the molecule is bent in solution. In advance of the structures of the receptor complexes, mutagenesis of the Fca/mR and FcmR domains, and of IgM-Fc and Fcm3-4 will be used to map the binding sites; the effects of these mutations will be valuable for later studies to modulate the individual activities to investigate functional mechanisms, or for engineering IgM for therapeutic purposes.

Planned Impact

This project will provide structural information on IgM-Fc in its monomeric and polymeric forms, and its interactions with complement (C1q), and immune receptors Fca/mR and FcmR. Since there are no high-resolution structural data for any part of IgM-Fc, this will have a substantial impact for all researchers interested in antibody structure and function. The need for such structures is highlighted by numerous modeling studies of IgM used to interpret functional data. Modeling of monomeric IgM as part of the B cell receptor for antigen has also been undertaken in order to understand B cell activation, and conformational change mechanisms proposed but without supporting structural data. The C1q and receptor binding sites in IgM-Fc are not known in detail, nor whether there is steric or allosteric interplay between them; this fundamental information will be valuable to all those interested in the functional roles of IgM or engineering IgM for therapeutic applications, including the pharmaceutical industry. The potential impact of this information may be judged by analogy with the extensive structural data on IgG-Fc and its receptors that has had considerable impact upon engineering IgGs for therapeutic application, and also our work on IgE-Fc and its receptors that has influenced development of anti-IgE and IgE/receptor inhibitors for allergic disease. At a more fundamental level, mutagenesis to remove C1q and receptor activities from IgM can be used to probe functional mechanisms, as has been done extensively for IgG and IgE.

It has only recently been appreciated that IgM plays such a critical role in immune defence, providing early protection against infectious pathogens, directing the secondary response and, through removal of apoptotic cells, restricting atherosclerosis and the development of autoimmunity. Most antibodies isolated from human serum with anti-cancer activity are unmutated IgMs, and their tumour survelliance role is also under investigation. Furthermore, the only IgM isotype-specific receptor, FcmR, was discovered just three years ago. Thus many communities of researchers involved in these diverse disease areas are now looking at IgM. In humans, IgM anti-phosphoryl choline (PC) antibodies constitute a strong protection marker for atherosclerosis, and in SLE patients, higher levels of IgM autoantibodies that recognize epitopes on dead and dying cells, such as PC, correlate with lower susceptibility to cardiovascular events. IgM causes ischaemic reperfusion injury (IRI), and understanding how to control complement activation is important to IgM's therapeutic applications.

There are several ways in which IgM can be used therapeutically. Firstly, it can be administered by i.v. injection, as is IgG; purified IgM from serum is used to prevent sepsis (Pentaglobin). A monoclonal human IgM against GM3 ganglioside on melanoma cells, expressed as both a recombinant pentamer and hexamer in CHO cells, has already undergone a Phase I clinical trial. Three antibodies with in vitro anti-tumor cell activity have been expressed, one as hexamer in a human cell line. Our results may suggest improvements for these therapeutic IgM antibodies in the way that binding sites on IgG for complement and FcgR have been engineered. Secondly, in IRI, where IgM antibodies have a detrimental effect, inhibitory mimetic peptides have been developed which bind to the IgM Fab; one outcome of our project might be mutations in, or peptides/small molecules that bind to, IgM-Fc. Thirdly, it has been suggested that IgM can be used as an adjuvant to boost vaccination against microbes. The alarming rise of bacterial resistance to antibiotics has renewed interest in antibody therapy and vaccination strategies.

There are thus potential benefits for public health and for pharmaceutical industry. We also have a track record of training scientists for industry: two ex-PhD students from the group now lead drug discovery projects in major UK companies.

Publications

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Nyamboya R (2020) Mapping of the binding site for FcµR in human IgM-Fc in Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Zhang X (2017) IgY: a key isotype in antibody evolution. in Biological reviews of the Cambridge Philosophical Society

 
Title Aperiodic tiling pattern 
Description Production of the largest aperiodic tiling pattern, through involvement of the public in printing the tiles and adding to the pattern. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact Sparked discussion about symmetry, structure and pattern in biology, which could then be related to our work, using X-ray crystallography, to study antibodies and allergens in allergic disease. 
 
Title Crystal Symmetry 
Description In collaboration with glass sculptor Dr. Shelley James, two exhibitions at the History of Science Museum, Oxford to celebrate the International Year of Crystallography. Exhibition consisted of graphic art pieces and glass sculptures representing aspects of crystallographic symmetry. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2014 
Impact Led to invitations to participate in public engagement activities and two public lectures at the History of Science Museum, Oxford, and at the Diamond Light Source as part of the CCP$ Summer School. 
 
Title DNAted at Fabrication Festival 
Description 3d sculpture created from linear (DNA) code; public interactive exhibit as part of the London Fabrication Festival, Somerset House. 
Type Of Art Artefact (including digital) 
Year Produced 2015 
Impact Several invitations for further opportunities for exciting and development of the project (with Mehran Gharleghi). 
 
Title Dynamic Symmetry 
Description In collaboration with glass sculptor Dr. Shelley James, exhibition of graphic art and glass pieces to illustrate aspects of crystallographic symmetry, at the Royal Society Summer Exhibition, London. A celebration of the International Year of Crystallography. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2014 
Impact Public engagement with crystallography; subsequent invitation by The Royal Society to give lecture at the Royal Society and run a pubic engagement activity as part of the Big Draw Event, October 2014. 
 
Title Gaze - seen and unseen worlds 
Description Glass sculptures; product of collaboration with artist Dr. Shelley James; exhibition at The Circus Gallery, London. 
Type Of Art Artefact (including digital) 
Year Produced 2015 
Impact Interest from various other galleries, organisations for hosting similar event. 
 
Title Glass sculptures by Dr. Shelley James 
Description Glass sculptures (and also multiple, smaller 3d-printed copies) of mirror symmetry-related crystals, to illustrate lectures on topic of mirror symmetry, handedness and pattern in biology. 
Type Of Art Artefact (including digital) 
Year Produced 2018 
Impact Sparked discussion about symmetry, patterns and structure in biology, which could then be related to our work using X-ray crystallography to study antibodies and allergens in allergic disease, including asthma. 
 
Title Minerva Scientifica Franklin Effect 
Description Music composition based upon crystals, symmetry and DNA structure, involving primary and secondary schools in Islington 
Type Of Art Composition/Score 
Year Produced 2016 
Impact Tweets/blog reports of the workshops and performance led to various enquiries for future events. Event featured as part of National Science Week. 
 
Title Spit Crystal: A Glance Within 
Description Set of 10 images of crystallisation patterns formed from salivary fluid. Produced by artist Inés Cámara Leret. 
Type Of Art Artwork 
Year Produced 2016 
Impact Successful sales of limited edition of this set of prints. 
 
Title The Franklin Effect: CD 
Description CD launched of new musical compositions by four women composers, inspired by the work of women scientists including Rosalind Franklin. Entitled: The Franklin Effect. Produced by Minerva Scientifica/Electric Voice Theatre 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2016 
Impact Excellent reviews in "The Gramophone" and "BBC Music Magazine" and elsewhere. Selected for live performance at The Edinburgh Festival 2016. 
 
Description IgM antibodies are not only the most primitive antibodies in evolutionary terms, but are the first to be produced in an immune response to infection. They play a critical role in providing a base level of protection, and also in initiating an immune response involving highly specific IgG antibodies, or an allergic response involving IgE antibodies. While we know much about the structure and function of IgG and IgE antibodies and their cell surface receptor interactions, very little is known about IgM, and nothing about the interactions with its receptors.

We produced various molecular fragments of IgM for the first time (e.g. IgM-Fc, Fcm3-4, hexameric IgM-Fc) as well as whole IgM, to investigate its structure using a range of biophysical techniques. Many of these studies were carried out in parallel with IgE antibody fragments for comparison, since we know much about IgE structure. In particular, IgE has an acutely bent structure in its Fc (receptor-binding) region, and undergoes conformational change upon receptor binding; this bend is critical for the unique allergy-related functional properties of IgE. Since IgM has the same number of domains in its Fc region, and is the evolutionary precursor of IgE, a key question is whether IgM-Fc has a similarly bent, or alternatively, an extended structure.

To this question we obtained a definitive answer: IgM-Fc does not adopt a bent structure, and in fact, in complete contrast to IgE, is fully extended. We determined this by small-angle X-ray scattering (SAXS) at the Diamond Light Source: IgM-Fc 100% extended (& Rg value 37.1Å); IgE-Fc 82% bent and partially bent, 18% extended (& Rg value 28.8Å). These results are currently being prepared for publication. Intriguingly, IgY-Fc, which is an evolutionary intermediate (in birds and reptiles) between IgM and IgE, showed intermediate results (65% extended and Rg value 36.7Å). Thus we have a structural perspective on the evolution of antibodies, and clearly IgM, while perhaps capable of conformational change, adopts an extended, planar structure, before any interaction with an antigen or a cell surface receptor.

We also measured the thermal stability of IgM-Fc and Fcm3-4 fragments (the latter lacking the two Cm2 domains) and again compared these with IgE-Fc fragments. In this regard, IgM is more stable than IgE (melting temperatures Tm: IgM fragments 58 and 72 deg.C; IgE fragments 52 and 64 deg.C), although these results show that it is the Cm3 domain in IgM, just as it is the Ce3 domain in IgE, that is the most thermally sensitive region of the antibody. (These results are being prepared for publication). In this respect the evolutionary relationship between the antibodies can be seen, and this information is important if IgM is to be developed as a format for therapeutic monoclonal antibody engineering.

We also expressed the single extracellular domain of the IgM receptor, FcmR, as a soluble protein, and determined (by surface plasmon resonance analysis) that it binds to IgM with a very weak affinity (micromolar Kd); we also showed that it binds to the Cm3-4 domains. This is the first mapping of a receptor interaction to IgM, and has now been followed up by mutagenesis; we have identified a key residue in the Cm4 domain and mapped the extent of the site (paper about be submitted). We hope that a crystal structure of the FcmR/IgM-Fc complex may also be achieved.

Finally, crystallisation trials of IgM-Fc were successful, but the crystals diffracted to rather low resolution (4.5Å, with high mosaicity), and a full structure determination was not possible. However, the very unusual unit cell (53 x 256 x 351Å), space group and 6-fold non-crystallographic symmetry (seen in a self-rotation function) led to a model of a hexameric array of IgM-Fc regions, mediated by contacts between the Cm4 domains, but only these domains could be located in the structure so far. These are exciting results because IgM naturally occurs as hexamers in serum. We are pursuing further crystallographic analysis and attempting improvement in the diffraction properties of the crystals, but this is a significant step towards a full structure determination of the IgM antibody molecule.
Exploitation Route Enhanced understanding of the basic structure and function of IgM will support immunological work in many fields, such as: the use of IgM as a format for monoclonal antibodies (for which there is growing interest in the pharmaceutical industry); the role of IgM in auto-immune disease (such as rheumatoid arthritis, RA); the role of receptor interactions in mediating both the beneficial (protective) and disease-related functional activities of IgM. The molecular fragments that we have generated will permit ourselves and others to pursue structural (X-ray crystallographic) studies of IgM/receptor complexes, which in the longer term may open up new therapeutic strategies for treating inflammatory disease such as RA.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Title IgM-Fc protein constructs 
Description Protein fragments comprising the complete Fc region of IgM (six domains) and the Fcm3-4 region (4 domains). 
Type Of Material Biological samples 
Provided To Others? No  
Impact Mapping of receptor binding site to Cm3 domain; comparative thermal stability measurements reveal Cm3 domain as the most thermally sensitive domain; subject for low resolution crystal structure analysis of IgM-Fc. 
 
Description Prof. H. Kubagawa 
Organisation University of Alabama at Birmingham
Country United States 
Sector Academic/University 
PI Contribution We are modelling the structure of the high affinity IgM Fc receptor and its interaction with IgM, incorporating our own mutagenesis data on IgM-Fc and Prof.Kubagawa's mutagenesis data on the receptor. We are also calculating the effect of receptor mutations on the thermostability of the receptor, for consideration with the the activity assay data of Prof. Kubagawa.
Collaborator Contribution Mutagenesis and activity data for various mutants of the high-affinity IgM receptor.
Impact Paper in preparation.
Start Year 2019
 
Description Allergy and Asthma talk at Medical Society St Paul's School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk about research into allergy and asthma prompted discussion about the science and careers in science and medicine.

Requests for placements and advice about university applications.
Year(s) Of Engagement Activity 2014
 
Description Atlas Project 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Interview about X-ray crystallography, crystallisation and structure analysis; reference to our work on antibodies in allergy and asthma.
Year(s) Of Engagement Activity 2018
 
Description Atlas Project Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation of crystallisation process of various substances from sea water to salivary fluid. Encouraged people to think about natural variation of environmental and medically relevant substances.
Year(s) Of Engagement Activity 2018
 
Description Brighton College - Protein Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact About 80 pupils involved in workshop at their school, plus talk, about protein structure and immunology.
Year(s) Of Engagement Activity 2013,2014,2015
 
Description Bush House, King's College London, The Science and Art of Mirror Symmetry. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Hands-on activity to explore symmetry in tiling patterns, mirror symmetry and aperiodic symmetry. Included one-hour lecture (repeated). All-day event in public accessible space. Sparked discussion about pattern, structure, molecular structure and the work with antibodies in allergy and asthma in which we are engaged.
Year(s) Of Engagement Activity 2018
 
Description Crystals, Symmetry and the DNA Double Helix 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture led to discussion about science: crystallography, DNA, symmetry and mathematics.

Requests for further talks and engagement activities and schools visits.
Year(s) Of Engagement Activity 2014
 
Description Exhibition: Viewing the Invisible 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The project involved sitting for sculptor and conversing about the similarities and differences between an artist's and a scientist's approach their work. Filmed the process and the conversation; exhibited results along with 6 other artist/scientist partners at Bush House Arcade, London; public lecture/workshop at The National Portrait Gallery. Expectation of further public exhibitions of the material.
Year(s) Of Engagement Activity 2019
 
Description Interview about Rosalind Franklin (Mars Rover naming; 07/02/19) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview with BBC Radio Wales and contribution to BBC TV (World News) explaining the role of Rosalind Franklin in the discovery of the structure of DNA, following the naming of the Mars Rover that will search for evidence of life on Mars.
Year(s) Of Engagement Activity 2019
 
Description Interview for "Technology Network" (22/06/18) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Interview and article about X-ray crystallography and structural biology.
Year(s) Of Engagement Activity 2018
 
Description Last Words (Ray Gosling) BBC Radio4 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invitations to further public engagement activities.
Year(s) Of Engagement Activity 2015
 
Description Pattern in African fabric design (12/02/19) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Contribution to a "King's Together" interdisciplinary project to explore pattern in African textile design; my contribution is to classify pattern and symmetry.
Year(s) Of Engagement Activity 2019
 
Description Photograph 51 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Prof. Brian Sutton acted as science advisor to the West End production of the play "Photograph 51" and was involved in several associated outreach events for schools.
Year(s) Of Engagement Activity 2015
 
Description Production of "Photograph 51" (Cambridge) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk and presentation of artefacts in the King's College London Archive to the cast and production team of a new production of "Photograph 51", a play by Anna Ziegler, in Cambridge in April 2019. The cast reported that they were inspired by their new-found understanding of X-ray diffraction, DNA and the scientists involved in the discovery of its structure.
Year(s) Of Engagement Activity 2019
 
Description Protein Folding Workshop at Brighton College 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Approximately 100 pupils attended the talk and activities, which promoted discussion about science and possible careers.

Led to requests for visits to King's College; placements for work experience.
Year(s) Of Engagement Activity 2013,2014
 
Description Public Lecture at Dulwich Picture Gallery 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk about crystallography and the discovery of the DNA structure prompted discussion about science, genetics, symmetry and mathematics.

Requests for visits to lab and careers in science.
Year(s) Of Engagement Activity 2014
 
Description Public talk (22/03/18 at Guy's Campus of KCL) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Talk about symmetry and molecular structure, in particular handedness (chirality) and its discovery. This was followed by a hands-on event, generating a quasi-periodic tiling pattern. Comments afterwards from many showed that a whole new way of looking at molecular structure had been opened up for them.
Year(s) Of Engagement Activity 2018
 
Description Public talk - Museum of Life Sciences, Guy's Hospital Campus, King's College London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk about DNA and symmetry in biology, to celebrate the 10th Anniversary of the Museum of Life Sciences.
Year(s) Of Engagement Activity 2019
 
Description Rosalind Franklin: Women in Science conference (Warwick University) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk about Rosalind Franklin and panel discussion in context of one-day symposium to highlight women in science; Warwick University.
Year(s) Of Engagement Activity 2016
 
Description Royal Society Summer Science Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Hands-on activity involving tiling patterns to present principles of symmetry, crystallography and structure analysis. Discussion of antibody structure, antibody recognition and allergic disease including asthma.
Year(s) Of Engagement Activity 2017
 
Description School Visit to KCL (The Grey Coat Hospital School) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit to labs; tour of other facilities relevant to our work in allergy and asthma; talks; time for free discussion.
Year(s) Of Engagement Activity 2017
 
Description School visit (Greycoat School 21/11/18) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk about DNA and role of Rosalind Franklin in the discovery of its structure.
Year(s) Of Engagement Activity 2018
 
Description School visit and workshop (St. Paul's Catholic College) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit to St. Paul's Catholic College; 6th form science students; talk and half-day workshop on protein structure, folding, mis-folding and disease.
Year(s) Of Engagement Activity 2016
 
Description School visits to labs 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 80 secondary school pupils attended day-long workshop on protein and DNA structure
Year(s) Of Engagement Activity 2015
 
Description Schools visits to research labs 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Over several schools visits, approx. 100 students attended demonstrations and visits to various research labs within the group, which prompted discussion about science and careers in science.

Requests for placements and advice about university applications.
Year(s) Of Engagement Activity 2011,2012,2013,2014
 
Description Science Gallery London: Spit Crystal Project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Art/science collaborative project entitled "Spit Crystal". Supported by Science Gallery London (based at King's College London) and working with artist Inés Cámara Leret, the project explored "ferning" crystallisation patterns from spit and salivary fluid. Open day events engaged public audiences with concepts of crystallography, crystals and X-ray diffraction, as well as the medical aspects of salivary fluids and the use of ferning as a potential biomarker for disease.

The project was selected for an international art/science event in The Netherlands.
Year(s) Of Engagement Activity 2016
 
Description Science Gallery London: YouTube video 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact YouTube video describing experiences of public engagement through Science Gallery London and featuring the Spit Crystal project.
Year(s) Of Engagement Activity 2017
 
Description Science Stories (Maurice Wilkins) BBC Radio4 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invitations to further public engagement activities.
Year(s) Of Engagement Activity 2015
 
Description Symmetry and Crystals Open Day, HSM Oxford 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 1400 attendees of day-long event. Stimulated discussion about various aspects of science: crystallography, symmetry and mathematics, medical science related to my research.

Subsequent correspondence; requests for lab visits; advice about scientific careers.
Year(s) Of Engagement Activity 2014
 
Description Symmetry, Crystals and DNA talk at Winchester College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 60 pupils attended talk, which stimulated discussion and thoughts about science careers.

Requests for work placements and advice about university applications.
Year(s) Of Engagement Activity 2014
 
Description Talk and hands-on tiling event (30/05/18) Bush House Arcade 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Hands-on event to generate a novel quasi-periodic tiling pattern involving tiles with handedness (chirality). Brief talk also delivered twice during the day. Considerable interest generated and discussions promoted about the nature of handedness, crystals and molecular structure, periodicity and quasi-symmetry.
Year(s) Of Engagement Activity 2018
 
Description Talk to Aldwych Quarter Project (25/07/18) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Talk about proposals for tiling patterns as part of the Aldwych Quarter development by Westminster City Council.
Year(s) Of Engagement Activity 2018
 
Description Talk to King's Designers (28/06/18) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Talk about symmetry, handedness and pattern. Many in the audience reported that they now viewed pattern and symmetry in an entirely new way.
Year(s) Of Engagement Activity 2018
 
Description Teachers' Conference (Royal Institution, London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Talk to science teachers' conference on symmetry, crystallography, structural biology in medicine; event run by OCR examination board; lecture and panel discussion. Event held at the Royal Institution, London.
Year(s) Of Engagement Activity 2016
 
Description The Franklin Effect: Primary Schools Workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Worked with Minerva Scientifica to deliver a series of three workshops combining music, dance, symmetry and science, the latter focussed on Rosalind Franklin, X-ray crystallography, DNA and evolution. Project selected as flagship event for British Science Week, March 2016.
Year(s) Of Engagement Activity 2016
 
Description The Hospital Club: Panel discussion 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Contributed talk (symmetry, crystallography, DNA, structural biology in medicine) and panel discussion to present an art/science collaboration between Brian Sutton and Shelley James (glass sculptor).
Year(s) Of Engagement Activity 2016
 
Description Video about Rosalind Franklin (06/12/18) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Video to explain role of Rosalind Franklin in the discovery of the structure of DNA, promoted by King's College London.
Year(s) Of Engagement Activity 2018
 
Description Visit of Greycoat School to King's 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk about Rosalind Franklin, crystallography and DNA. About 50 sixth-form pupils attended. Questions, excited discussion about scientific research, and school reported increased interest in related science subjects.
Year(s) Of Engagement Activity 2019
 
Description Work experience visits 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact About 6 school pueblos in total visited for several days to gain work experience.
Year(s) Of Engagement Activity 2013,2014,2015