Reconstructing the genomic network that coordinates cell polarity and the cell cycle, using microscopy-based functional genomics

Lead Research Organisation: University of Cambridge
Department Name: Genetics

Abstract

An extraordinary capacity of all cells - from the simpler yeast cells to the most complex nerve cells in our bodies - is that to control space and time. In space, cells become asymmetrically polarized and adopt specialized shapes and growth modes both tailored and essential for the functions they need to perform; through time, cells make continually decisions as to when to grow or when to divide. Not surprisingly, when cells lose control over space or time they begin to malfunction, as is the case of metastatic cancerous cells that erratically conquer, grow and divide in wrong parts of the body at the wrong time.

Three decades of outstanding biomedical research have identified the molecular gearboxes that control cellular polarity ('space') and the cell division cycle ('time'), yet how those two fundamental processes are coordinated is virtually unknown. A better knowledge of that coordination could significantly advance our understanding of how cells and organisms live healthily and open the way to novel strategies for combatting a battery of diseases. What genes and proteins secure the coordination of polarity and the cell cycle, to secure for example that cells do not divide while they grow and vice-versa? Do they all constitute one single molecular machinery that acts together to secure cell polarity and cell cycle coordination, or do various submachineries exist that are exploited by cells in different situations? And what insights can those machineries give as to the origin of diseases like cancer and how to combat them?

These are questions that we aim to address with this project, where we will combine cutting-edge genetics, microscopy and computational functional genomics methods to investigate the coordination of cell polarity and the cell cycle in unprecedented detail.
The evolutionarily conserved molecular gearboxes that regulate cell polarity and the cell cycle were both largely discovered using the yeasts as experimental organisms, as they can be easily genetically manipulated and studied under the microscope. Therefore, in this project we will build upon that work and exploit the power of the yeast system and of state-of-the-art technologies to systematically explore the yeast genome and enquire which genes coordinate polarity and the cell cycle, using a commercial collection of 3700 yeast lines lacking each gene in the genome readily available in our laboratory. We have developed a genetic tool that allows us to monitor precisely the polarity status of each cell and simultaneously its cell cycle state. We will introduce that so-called 'cell polarity/cell cycle (CP/CC) biosensor' in the 3700 yeast lines, and image them using a robotized high-resolution OperaLX microscope - the only one in the market with the required throughput and resolution - and analyze all the images generated using automated image analysis computer programmes. These are protocols that our laboratory has pioneered, putting us in a unique position to carry out this project and address these questions for the very first time.

Lastly, we will identify which of the genes found to coordinate cell polarity and cell cycle in yeast also function analogously in cultured human cells and whether mutations in those genes are found to be enriched in cancer/diseases databases, indicating they may be used as leads for the design of future therapeutics.

Technical Summary

Cell polarity and the cell cycle are two fundamental biological processes whose deregulation leads to countless pathologies, including cancer. Decades of research - notably in yeast - have discovered the molecular gearboxes controlling each of those processes, yet it is virtually unknown how they are molecularly coordinated. This project aims to comprehensively identify for the first time genes and proteins that coordinate cell polarity and the cell cycle using an integrated Systems Biology approach - combining genetics, systematic gene knockouts, high-throughput/high-content microscopy and computational/bioinformatics methods - and the fission yeast (Schizosaccharomyces pombe) as model organism.

In S. pombe, cell polarity and cell cycle progression are tightly correlated. We developed a 'biosensor' - CRIB-mCherry (a protein that interacts with active Cdc42) co-expressed with Cdc13-GFP (Cyclin B) - that allows us to simultaneously assess under the microscope the cell polarity and cell cycle (CP/CC) state of S. pombe cells and cell populations. We will generate a genome-wide collection of knockout yeast strains expressing the 'CP/CC biosensor', image the collection using high-throughput confocal microscopy and use custom-developed image analysis/Machine Learning tools to quantitate the biosensor signal from all knockouts and identify those with abnormal polarity, abnormal cell cycle, or both.

Using bioinformatics, we will then seek to clarify how the genes (corresponding to the knockouts identified) regulate CP/CC coordination by linking them to existing pathways of cell polarity and the cell cycle, and investigate their relevance for diseases in particular cancer. We will then experimentally validate and characterize the identified CP/CC coordinating genes in yeast. Finally, we will test whether their orthologues also play a similar role in human cultured epithelial cells, providing the first examples of such genes for humans.

Planned Impact

The proposed research will lead to advances that could impact not only the scientific community but also a number of non-academic beneficiaries:

POTENTIAL IMPACT FOR HEALTH AND THE GENERAL PUBLIC.
- Through this project, new and deep knowledge will be gained with regards to the fine coordination of cell polarity and cell division - two fundamental biological processes of medical relevance - by identifying for the first time families of genes and proteins coordinating those processes and clarifying how those genes/proteins participate in cancer or disease pathways. This will generate a wealth of information that could in the longer term inspire novel therapeutics for the long-term benefit human health and the general public.

IMPACT FOR THE BIOTECHNOLOGY AND PHARMACEUTICAL INDUSTRY
Many of the technological tools developed in this project could have potential uses for the biotech and pharmaceutical industries.
- Due to the conserved molecular mechanisms that govern cell cycle and cell polarity in yeast and humans, our yeast strain expressing the cell polarity/cell cycle (CP/CC) biosensor could be directly exploited as a tool for chemical screening to identify molecules able to interfere with cell polarity, cell cycle progression or the coordination of both, helping to select for potential anti-cancer drugs.
- Moreover, an analogous CP/CC biosensor could also be developed for human cells and CP/CC biosensor-expressing human cell lines established. Building upon our validation work with human cells (section 4.6), this could enable partial or genome-wide RNAi screening for human cell-specific CP/CC genes, as well as screening libraries of drugs and chemical compounds capable of interfering with the machineries that coordinate cell polarity/cell cycle or conversely capable of reverting the lack of their coordination in selected cancer/disease cell lines. Both these could be of interest to the drug industry.
- Some of the computational tools and algorithms that we will develop - for multi-dimensional phenotypic (morphology/fluorescence) profiling; bioinformatics and statistical network inference; etc - could be adapted for the design of research or medical diagnostic tools. For example, based on our validation work with human cells (section 4.6) we could adapt our custom-made algorithms to quickly recognize aberrant cell polarity/cell cycle signatures of cell populations, to quickly analyze or compare pathological tissue samples, suggest possible molecular pathways involved in the pathologies, etc.
- Advances in software for image and data management, analysis or integration with data analysis frameworks and with online databases could similarly be of interest in a wide range of applications for biomedical/biotechnology companies, for high-throughput/high-content screening, medical imaging and diagnostics, and others.

BENEFITS TO SOCIETY/ETHICS
- Finally, today there is a strong demand to replace animal experiments with invertebrate model systems and cell culture assays because of the societal and ethical problems that animal experimentation raises. By using yeast and human cells to molecularly dissect the machineries that coordinate cell polarity and the cell cycle - two fundamental biological processes whose deregulation leads to many pathologies including cancer - our work will contribute to the advancement of this important area of research, while addressing Replacement and related pressing societal problems.
 
Description In this project we have sought to identify with unprecedented detail the network of genes that control and coordinate two fundamental cell biological properties: cell polarity and the cell cycle. We have done this by combining a range of interdisciplinary methods including cutting-edge genetics, microscopy and computational functional genomics strategies.

Specifically, our approach has been to exploit the power of yeast as experimental model system and of those state-of-the-art technologies to systematically explore the yeast genome and enquire which genes coordinate polarity and the cell cycle, using a commercial collection of 3700 yeast lines lacking each gene in the genome readily available in our laboratory. Using a genetic tool we developed that we call the 'cell polarity/cell cycle (CP/CC) biosensor', which allows us to monitor precisely the polarity status of each cell and simultaneously its cell cycle state, we introduced that biosensor in the entire library of 3700 yeast lines, imaged them using a robotized high-resolution OperaLX microscope - the only one in the market with the required throughput and resolution - and analyzed all the images generated using automated image analysis computer programmes using protocols that our laboratory has pioneered.

Thus far, we have identified as proposed a few hundreds of new genes involved in cell polarity, cell cycle, or both processes, and are now in the course of selecting a few dozens among them for further characterization and for publication of a manuscript providing our main findings and a genomic resource of images and cell lines for the community.

Our original intention was to complete that project within three years, however because my lab moved location and because key people left the project along the way we have taken delay. We aim to complete it in 2016 even if not funded anymore by the BBSRC.

When completed this BBSRC funded project will make available:
1) Lists of tens of novel genes involved in controlling cell polarity, cell cycle, or both
2) A genome wide library of yeast knockout cell lines expressing a 'cell polarity/cell cycle (CP/CC) biosensor' allowing the simultaneous monitoring of cell polarity and cell cycle state across 3700 different yeast mutants
3) A repository of images and phenotypic annotations for those 3700 genotypic conditions made available online for the entire community, building on a similar repository we established in a related project http://www.sysgro.org/ .

However, even if our main project with this BBSRC grant is not completed, we have managed through the people employed by this grant to contribute to a few accomplishments (papers acknowledging the BBSRC support mentioned for each project):

A) Completing the establishment of a high-throughput/high-content microscopy (HT/HCM) phenotyping platform for yeast functional genomics, one of the most advanced platforms worldwide and a source of increasing local/international collaborations (published in Jeffares et al, Nature Genetics 2015).
B) Systematically identifying genes controlling cell shape, microtubules and cell cycle progression. With our HT/HCM platform, we identified/annotated 262 genes controlling those processes, with 62% newly implicated in them and 35% involved in multiple processes (published in Graml et al, Developmental Cell 2014; online resource at http://www.sysgro.org/). Additionally, we discovered a potentially biomedically-relevant role for the ATM/ATR-mediated DNA damage response in microtubule control.
C) Wiring the yeast cell polarity network. We identified bioinformatically core factors regulating polarity in S.pombe (published in Vaggi et al, PLoS Computational Biology 2012), and used HT/HCM to systematically identify pairwise interactions between them, to generate a picture of the polarity network and its re-wiring through the cell cycle (Dodgson et al, in preparation).
D) Identifying new polarity control layers. We discovered that polarity regulators localize to 50-100nm clusters at the cell cortex, a feature required for polarity control (published in Dodgson, et al, Nature Communications 2013). We also discovered that inhibition of Cdc42 Rho-GTPase activity by ERM-related factors is needed for polarity plasticity (Geymonat et al., in consideration, eLife).
E) Clarifying how mechanics affects cell proliferation. We found that in yeast cell shape conditions future shape and proliferation via the cell wall mechanics (published in Abenza et al, PLoS ONE 2014 and in Abenza et al, Nature Communications 2015; and Abenza et al, in preparation for Lab on a Chip).
F) Given our work's highly interdisciplinary nature, we also developed a computational framework to optimally identify scientists with whom to network at scientific conferences (published in Vaggi et al, eLife 2014) which gathered a lot of media attention (Times Higher Education, Harvard Business Review).
G) In addition, we developed a new visual analytics tool named Mineotaur (published in Antal et al, Genome Biology 2015; online at http://www.mineotaur.org/) for empowering the entire community, computational and non-computational alike, to continue mining the primary data from microscopy based phenomics projects like the project in B.
Exploitation Route When completed, in addition to associated outputs listed as published key findings, this BBSRC funded project will make available:

1) Lists of tens of novel genes involved in controlling cell polarity, cell cycle, or both

2) A genome wide library of yeast knockout cell lines expressing a 'cell polarity/cell cycle (CP/CC) biosensor' allowing the simultaneous monitoring of cell polarity and cell cycle state across 3700 different yeast mutants

3) A repository of images and phenotypic annotations for those 3700 genotypic conditions made available online for the entire community, building on a similar repository we established in a related project http://www.sysgro.org/ .

These are going to provide discoveries and ample online and experimental resources for the community to build on our work.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Cambridge Cancer Centre Pump Priming Grant
Amount £62,000 (GBP)
Organisation Cambridge Cancer Centre 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 09/2016
 
Title Mineotaur: a tool for high-content microscopy screen sharing and visual analytics. 
Description A key for the future of biomedicine is the capacity to overcome our present deluge of biological Big Data and turn it into a catalyzer of precise, predictive and personalized treatments. Yet we are far from that, with most large-scale biomedical data being mined mostly by computational scientists, a very reduced subset of the community with high expertise in computing but very little expertise in most other relevant biomedical areas. As an example, although microscopy phenomics projects generate powerful data on intracellular information at the single cell level for thousands of genotypic conditions, accessing that data requires specialized image/data analysis knowledge, which means most often that data is no longer mined after publication, contributing to an ever increasing data overflow. For this reason, my group is increasingly investing in developing online visual-analytics tools to potentiate the return-on-investment of those projects, specifically by allowing non-computational scientists to access and mine large (>million points) microscopy-based screen datasets via easy-to-use online interfaces, effectively crowd-sourcing the analysis. The first such tool is called Mineotaur (http://www.mineotaur.org/), and is going to be integrated in the forthcoming Image Data Repository (http://www.bbsrc.ac.uk/news/research-technologies/2015/150213-pr-collaborations-tackle-bioscience-big-data.aspx; see demo at http://idr-demo.openmicroscopy.org/webclient/userdata/?experimenter=-1), an EBI/ELIXIR-hosted community resource that we are establishing since January 2015 in collaboration with Jason Swedlow (OME/Dundee) and Alvis Brazma (EBI/ELIXIR). 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact Early to be assessed 
URL http://www.mineotaur.org/
 
Title Image Data Resource (IDR) 
Description The largest community driven online biological imaging data resource in the World. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact A major new resource very broadly available to the entire community through EMBL EBI with >1.5 million experiments and >44 reference imaging datasets from the World. 
URL http://idr.openmicroscopy.org/
 
Title Mineotaur.org 
Description A visual analytics online tool and platform for large scale biological image data analytics 
Type Of Material Data analysis technique 
Year Produced 2015 
Provided To Others? Yes  
Impact implemented further in IDR resource in the EMBL EBI (separate entry) 
URL http://www.mineotaur.org
 
Title SYSGRO 
Description This community resource contains phenotypic annotations from genome-wide, high-throughput/high-content microscopy screens using the fission yeast Schizosaccharomyces pombe as model species. 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact SYSGRO represents the first microscopy phenotypic database for the major model species S. pombe. In fact, it is one of the very few microscopy phenotypic databases of its kind worldwide (another example is MitoCheck). In only two weeks from its publication, SYSGRO already attracted 1097 visits with 22.4% return visitors worldwide. In the coming month, it is going to be formally linked with Pombase (we have been preparing for that for the past 1.5 years), which is the sole genome curation database for this major model species. I anticipate that because of all of these reasons it is going to become a very high impact resource for the community and field. 
URL http://www.sysgro.org/
 
Description Attila Csikasz-Nagy Group 
Organisation Edmund Mach Foundation
Country Italy 
Sector Charity/Non Profit 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes computational/bioinformatics expertise.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Attila Csikasz-Nagy Group 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes computational/bioinformatics expertise.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Attila Csikasz-Nagy Group 
Organisation Microsoft Research
Country Global 
Sector Private 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes computational/bioinformatics expertise.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Attila Csikasz-Nagy Group 
Organisation University of Trento
Department Centre for Computational and Systems Biology
Country Italy 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes computational/bioinformatics expertise.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Eugenia Piddini Group 
Organisation University of Cambridge
Department Gurdon Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution In this collaboration we (= my team) contribute quantitative experimental expertise, in particular quantitative microscopy and image processing as well as statistical analysis.
Collaborator Contribution In this collaboration my collaborator's team contributes largely animal (particularly, human) cell culture expertise.
Impact One publication listed in the BBSRC output has profited from this collaboration: 25373780 (Oct, 2014) A Genomic Multiprocess Survey of Machineries that Control and Link Cell Sha...
Start Year 2012
 
Description Eugenia Piddini Group 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution In this collaboration we (= my team) contribute quantitative experimental expertise, in particular quantitative microscopy and image processing as well as statistical analysis.
Collaborator Contribution In this collaboration my collaborator's team contributes largely animal (particularly, human) cell culture expertise.
Impact One publication listed in the BBSRC output has profited from this collaboration: 25373780 (Oct, 2014) A Genomic Multiprocess Survey of Machineries that Control and Link Cell Sha...
Start Year 2012
 
Description Jürg Bähler Group 
Organisation University College London
Department Division of Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute high-throughput/high-content microscopy expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes various aspects of functional genomics expertise.
Impact One manuscript in second revision in Nature Genetics.
Start Year 2013
 
Description Jacques Dumais Group 
Organisation Adolfo Ibáñez University
Country Chile 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes expertise in biophysics and modelling in silico.
Impact Paper in preparation and nearly ready for submission
Start Year 2011
 
Description Jacques Dumais Group 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes expertise in biophysics and modelling in silico.
Impact Paper in preparation and nearly ready for submission
Start Year 2011
 
Description Masamitsu Sato Group 
Organisation University of Tokyo
Country Japan 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise, in particular high-throughput/high-content and quantitative microscopy.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes expertise in genetics and molecular biology, and provides cell lines to my group.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Masamitsu Sato Group 
Organisation Waseda University
Country Japan 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise, in particular high-throughput/high-content and quantitative microscopy.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes expertise in genetics and molecular biology, and provides cell lines to my group.
Impact Two publications listed in the BBSRC output: 24497549 (2014) A network approach to mixing delegates at meetings. 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ... have profited from this collaboration.
Start Year 2009
 
Description Pietro Cicuta Group 
Organisation University of Cambridge
Department Cavendish Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes microfabrication and biophysics expertise.
Impact No outputs from this yet
Start Year 2010
 
Description Pietro Cicuta Group 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes microfabrication and biophysics expertise.
Impact No outputs from this yet
Start Year 2010
 
Description Steve Jackson Group 
Organisation University of Cambridge
Department Gurdon Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes mammalian cell culture and DNA damage pathway expertise.
Impact One publication listed in the BBSRC output has profited from this collaboration: 24598026 (Aug, 2014) Rolled-up functionalized nanomembranes as three-dimensional cavities for si...
Start Year 2012
 
Description Susan Cox 
Organisation King's College London
Department Randall Division of Cell & Molecular Biophysics
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration was multidisciplinary, where we (= my team) contributed quantitative experimental expertise.
Collaborator Contribution This collaboration was multidisciplinary, where my collaborator's team contributed expertise in super resolution and microscopy.
Impact One publication listed in the BBSRC output has profited from this collaboration: 123673619 (2013) Spatial segregation of polarity factors into distinct cortical clusters is ...
Start Year 2012
 
Description Thomas Walter 
Organisation Curie Institute Paris (Institut Curie)
Country France 
Sector Academic/University 
PI Contribution This collaboration is multidisciplinary, where we (= my team) contribute quantitative experimental expertise.
Collaborator Contribution This collaboration is multidisciplinary, where my collaborator's team contributes computer vision/machine learning expertise.
Impact One publication listed in the BBSRC output has profited from this collaboration: 25373780 (Oct, 2014) A Genomic Multiprocess Survey of Machineries that Control and Link Cell Sha...
Start Year 2012
 
Title Mineotaur: a tool for high-content microscopy screen sharing and visual analytics. 
Description A key for the future of biomedicine is the capacity to overcome our present deluge of biological Big Data and turn it into a catalyzer of precise, predictive and personalized treatments. Yet we are far from that, with most large-scale biomedical data being mined mostly by computational scientists, a very reduced subset of the community with high expertise in computing but very little expertise in most other relevant biomedical areas. As an example, although microscopy phenomics projects generate powerful data on intracellular information at the single cell level for thousands of genotypic conditions, accessing that data requires specialized image/data analysis knowledge, which means most often that data is no longer mined after publication, contributing to an ever increasing data overflow. For this reason, my group is increasingly investing in developing online visual-analytics tools to potentiate the return-on-investment of those projects, specifically by allowing non-computational scientists to access and mine large (>million points) microscopy-based screen datasets via easy-to-use online interfaces, effectively crowd-sourcing the analysis. The first such tool is called Mineotaur (http://www.mineotaur.org/), and is going to be integrated in the forthcoming Image Data Repository (http://www.bbsrc.ac.uk/news/research-technologies/2015/150213-pr-collaborations-tackle-bioscience-big-data.aspx; see demo at http://idr-demo.openmicroscopy.org/webclient/userdata/?experimenter=-1), an EBI/ELIXIR-hosted community resource that we are establishing since January 2015 in collaboration with Jason Swedlow (OME/Dundee) and Alvis Brazma (EBI/ELIXIR). 
Type Of Technology Webtool/Application 
Year Produced 2015 
Impact Early to be assessed 
URL http://www.mineotaur.org/
 
Company Name CL-IC Technologies Limited 
Description The Cambridge-based company CL-IC Technologies Ltd (http://www.cl-ic.com/) offers professional speed networking services to both corporate and academic conference organisers. 
Year Established 2014 
Impact Just founded
Website http://www.cl-ic.com/
 
Description Cambridge Alumni Festival 2014 titled Engineering interdisciplinarity 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The talk indeed sparked an exciting Q&A afterwards.

I was thanked by members of the public who told me I opened their eyes altogether to our line of research
Year(s) Of Engagement Activity 2014
URL http://www.alumni.cam.ac.uk/sites/www.alumni.cam.ac.uk/files/documents/Alumni-Festival-2014-events-l...
 
Description Invited panelist: Open Data - moving science forward, or a waste of time and money? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I was invited panelist in the debate "Open Data - moving science forward, or a waste of time and money?" about the future of Open Data in biomedicine. The panelists invited were:
• Rafael Carazo-Salas, Group Leader, Department of Genetics, University of Cambridge
• Sarah Jones, Senior Institutional Support Officer, Digital Curation Centre
• Frances Rawle, Head of Corporate Governance and Policy, Medical Research Council
• Tim Smith, Group Leader, Collaboration and Information Services, CERN/Zenodo
• Peter Murray-Rust, Molecular Informatics, Department of Chemistry, University of Cambridge. ContentMine

The Panel Discussion took place 4 November 2015, Engineering Department, University of Cambridge, Cambridge, UK.
Year(s) Of Engagement Activity 2015
URL https://upload.sms.cam.ac.uk/media/2113537
 
Description Podcast Interview for The Naked Scientists 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I have been contacted by colleagues afterwards

I have been contacted by colleagues afterwards and hence it has given good visibility to our research
Year(s) Of Engagement Activity 2014
URL http://www.thenakedscientists.com/HTML/podcasts/specials/show/20141031-1/
 
Description Press Release for Developmental Cell paper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact My group's first major functional genomics article (http://www.cell.com/developmental-cell/abstract/S1534-5807%2814%2900591-7) and resource (http://www.sysgro.org) were just published in the journal Developmental Cell. The journal dedicated the issue cover (http://www.cell.com/developmental-cell/issue?pii=S1534-5807%2814%29X0021-3) to highlight our work.

In two weeks we have had over 1400 page views already. I anticipate this resource and press release are going to have important impact.
Year(s) Of Engagement Activity 2014
URL http://www.cam.ac.uk/research/news/imaging-the-genome-cataloguing-the-fundamental-processes-of-life
 
Description Press Release for Elife paper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I co-developed a computational approach that based on pre-existing information about conference attendees maximises their useful/fruitful interaction in speed networking events.

The key concepts behind it were published in a feature article of the multidisciplinary journal eLIFE (http://elifesciences.org/content/3/e02273) and attracted significant interest from the press (Times Higher Education http://www.timeshighereducation.co.uk/news/speed-dating-helps-conference-academics-mix/2011517.article, Harvard Business Review https://hbr.org/2014/03/algorithms-can-save-networking-from-being-business-card-roulette/?utm_source=Socialflow&utm_medium=Tweet&utm_campaign=Socialflow, etc) and all around internet. The University of Cambridge also wrote its own press release.


As before, our work attracted significant interest from the press (Times Higher Education http://www.timeshighereducation.co.uk/news/speed-dating-helps-conference-academics-mix/2011517.article, Harvard Business Review https://hbr.org/2014/03/algorithms-can-save-networking-from-being-business-card-roulette/?utm_source=Socialflow&utm_medium=Tweet&utm_campaign=Socialflow, etc) and all around internet. The original article has already had over 10000 views.
Year(s) Of Engagement Activity 2014
URL http://www.cam.ac.uk/research/news/meet-your-match-using-algorithms-to-spark-collaboration-between-s...
 
Description Wellcome Trust Advanced Course on genome-wide approaches with fission yeast, 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Informed ~50 professionals about new pioneering technologies we have continued developing in functional genomics.

Visibility for our work and requests to share our new technologies.
Year(s) Of Engagement Activity 2013
URL http://www.wellcome.ac.uk/education-resources/Courses-and-conferences/Advanced-Courses-and-Scientifi...