Integrative Biological Imaging Network (IBIN)

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

Abstract

To understand and combat the causes of human disease, we must understand the basic structure and function of the individual cells that make up the tissues and organs of the human body. For example, to allow the design of effective therapies to target cancer we first need to answer fundamental questions about how the growth, division and movement of cells are controlled. Robert Hooke was the first to use microscopes to describe cell structure in 1665, and since then microscopy has become one of the most powerful tools for cell biologists across the world. The power of light microscopes has of course continued to increase since their invention but, remarkably, the most dramatic improvement has come in the last ten years or so. In that period physicists have worked out how to measure the location of a single protein in a cell with a precision about ten times better that was previously thought possible. This is important because we can now see the internal structure and organisation of cells in much more detail. In parallel, physicists working together with biologists developed microscopical methods that, instead of just producing a map of the locations of one particular protein inside a cell, can produce a map of precisely where one protein is bound to another. This is a fundamental advance, because cell function is controlled by pathways and networks of such interactions between specific proteins. Potentially these new microscopes provide a window into the internal workings of a cell that allow us to see these protein networks. However, at the moment, the most detailed images can only be obtained from chemically preserved rather than living cells, and each image takes minutes to record. This is a serious problem, because the interactions between proteins that control cell function take place on the time scale of seconds and can occur at different places inside living cells. These methods are also currently restricted to looking at these molecules in single cells, not populations of cells. This provides very limited understanding of how cells communicate within tissues, and how these processes go wrong in different disease settings.

In the present proposal, biologists, physicists, chemists and mathematicians will work together as a team to develop new technology and approaches to image events that occur in live cells within 3-dimensional tissues. By combining ideas from different scientific backgrounds, we will be able to develop novel ways to tackle these problems and train scientists in a range of different types of techniques so they are equipped with key skills to perform innovative new experiments. We think that these new developments will unlock the potential of microscopy to show us how cells work at the molecular level and provide ways for us to analyse how cells work in normal healthy tissues as well as in diseases.

Technical Summary

The ability to image multiple signalling and phenotypic changes across different cell populations in vitro or in vivo, and then integrate and display this information quantitatively, would transform the study of many biological processes. Achieving such imaging and analysis is a major multidisciplinary challenge across the life and physical sciences, which holds the potential to deliver significant impact across a broad range of fundamental and medical fields. The Integrated Biological Imaging Network (IBIN) will combine cell, molecular and in vivo biologists, engineers, physicists, chemists and computational scientists to brainstorm and implement solutions to defining complex tissue-wide biological questions. The combined expertise in microscopy instrument development, cell and in vivo biology, mathematics, chemistry and computer science will provide an excellent framework to develop new strategies to tackle this unmet need. The shared vision is to develop a suite of multi-modal imaging approaches and appropriate biological tools/probes for use in these settings, which will deliver novel biological network information from molecules to mice. Quantitative information on protein dynamics, activation and interactions over this range of length-scales will allow us to understand the short and long term consequences of local signals on cell behaviour, tissue organisation and disease. We will base network discussions and experimental activities around three exemplar biological challenges that encompass the core problems to be tackled, with relevance to both homeostasis and disease mechanisms in the following biological areas: 1) Cell adhesion signalling hierarchy in development and disease; 2) Long-range molecular cues that regulate immune cell behaviour; 3) Tissue mechanics controlling cell growth. IBIN represents an exciting and timely opportunity to harness the broad base of UK expertise to deliver innovative new imaging solutions for complex biological questions.

Planned Impact

We anticipate that IBIN outcomes will provide impact in the following three areas:

Academic:
All network members will benefit directly from the opportunity to talk to people within their discipline who they might not otherwise meet, and across discipline barriers, leading to publications, collaborations and grant applications. Development of the individual techniques and enhanced integration will also benefit the broader scientific community. In addition to the network meetings, we will hold smaller network meet-ups at major conferences. Local network champions will promote the network at local group meetings across the UK. Understanding an order of magnitude change in length-scale and environment is a new frontier, with important biomedical implications.

Industry:
Immediate beneficiaries will be the instrument companies are already involved in the network; they will learn about complex biological questions and the methods that can tackle them, which is an area of considerable developmental interest for industry. We will also engage with other imaging hardware and life sciences companies as the network develops. Thus there are significant direct commercialisation opportunities for software and hardware solutions that emerge from network. Pharmaceutical companies will be key longer-term beneficiaries as the network activities provide broader understanding of the consequences of molecular events at the system level and provide more refined drug discovery approaches. Many of the network members have long-term collaborations with the Pharmaceutical industry and will therefore be very well placed to engage with these stakeholders as the network progresses to identify shared interests and collaboration opportunities.

Dissemination:
Our primary forms of dissemination of network activities will be through shared publications, presentation at external conferences and via our Network organised conference (also open to non-network members) in year 3 of this proposal. We will also ensure local dissemination occurs within Network institutions to identify new potential partners and also to publicise the work we are doing. We will establish a network website to update on network activities and provide means to rapidly feedback useful information to the scientific community and public. Within this we will embed an Online Network forum for virtual conferences and webinars between network members and industrial partners to share ideas and seek advice. If successful we will consider opening this out to non-network members as a core means to promote knowledge exchange. White papers and protocols emerging from the network discussions and activities will be disseminated via publications and made available on-line. We will organise pre-congress sessions at international conferences as well as promotion at exhibitions and networking events. To share our work with the general public, we will set-up 'Microscopy Live' events to encompass live broadcast of talks and demo's via the forum for public engagement. The visualisation of the otherwise invisible world is also an exciting and very appropriate area to engage the public and we will showcase the Network activities through events such as the Royal Society Summer Science Exhibition and 'Pint of Science' events.

Publications

10 25 50
 
Description First IBIN network meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact We held the first annual IBIN workshop, attending by ~100 participants from a wide range of disciplines (biology, chemistry, computational image analysis, physics). The workshop was focused around group discussions and brainstorming ideas to design new collaborations to tackle key emerging challenges in 3D bioimaging. Following the workshop, we have initiated a call for pump-priming, secondment and short term visit proposals to enable the ideas developed to be put into action.
Year(s) Of Engagement Activity 2019
URL https://ibin.org.uk/