Technology Touching Life Consultation

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#In genomics and proteomics, we are on the cusp of a revolution. With critical advances in DNA sequencing and proteomic technology, most individual humans, domesticated animals and will soon their genomes sequenced, and their gene expression and protein abundance and modifications profiles mapped and know. The impact of having, for example, the gene expression and protein abundance profile of many different tissues in an organism, the different parts of a tumour, or the full lifecycle of an important food source can only be dimly imagined. It is very likely that this data when combined with other information (as described below) can lead to many important fundamental discoveries, diagnostics, and new therapeutic approaches for many modern diseases. Personal DNA sequencing is potentially a quite lucrative commercial market as well and the availability of affordbable genome sequencing will open up a large number of commercial opportunities. The resources to fund the development of new gene sequencing and protein profiling technology, which will require innovations in chemistry, engineering and data analysis should be considered a major strategic scientific, social and commercial priority.  This will make good on the promise of this revolution and ensure the UK is a prominent player on the world stage in these domains.
#In genomics and proteomics, we are on the cusp of a revolution. With critical advances in DNA sequencing and proteomic technology, most individual humans, domesticated animals and will soon their genomes sequenced, and their gene expression and protein abundance and modifications profiles mapped and know. The impact of having, for example, the gene expression and protein abundance profile of many different tissues in an organism, the different parts of a tumour, or the full lifecycle of an important food source can only be dimly imagined. It is very likely that this data when combined with other information (as described below) can lead to many important fundamental discoveries, diagnostics, and new therapeutic approaches for many modern diseases. Personal DNA sequencing is potentially a quite lucrative commercial market as well and the availability of affordbable genome sequencing will open up a large number of commercial opportunities. The resources to fund the development of new gene sequencing and protein profiling technology, which will require innovations in chemistry, engineering and data analysis should be considered a major strategic scientific, social and commercial priority.  This will make good on the promise of this revolution and ensure the UK is a prominent player on the world stage in these domains.
#Imaging delivers measures the molecular and structural composition of biological and biomedical entities.  Most importantly, many imaging modalities are capable of measurements in space and time. Imaging systems that provide spatio-temporal map, when combined with spectroscopic capabilities that reveal probe environment allows different components using a variety of spectral and or probe technologies means that it is now routine to probe the molecular and structural makeup and dynamics of biological systems. In the future by combining the physical and life and biomedical sciences we can foresee the development of new imaging modalities where most of texture combined with the spatio-temporal resolution to reveal chemical physical composition and dynamics that have to date not been available. Overall, imaging technology in the 21st century depends on the combination of development of new probes for revealing molecular and structural composition and new detection modalities for revealing the composition of biomedical systems. Some examples of imaging "sweetspots":
#Imaging delivers measures the molecular and structural composition of biological and biomedical entities.  Most importantly, many imaging modalities are capable of measurements in space and time. Imaging systems that provide spatio-temporal map, when combined with spectroscopic capabilities that reveal probe environment allows different components using a variety of spectral and or probe technologies means that it is now routine to probe the molecular and structural makeup and dynamics of biological systems. In the future by combining the physical and life and biomedical sciences we can foresee the development of new imaging modalities where most of texture combined with the spatio-temporal resolution to reveal chemical physical composition and dynamics that have to date not been available. Overall, imaging technology in the 21st century depends on the combination of development of new probes for revealing molecular and structural composition and new detection modalities for revealing the composition of biomedical systems. Some examples of imaging "sweetspots":
-
##There are several labs developing imaging using mass spectrometry where isotopic analysis is used to reveal the chemical makeup of biomedical systems. Full development of mass spectrometric imaging (MSI), to include labeled probes labeled with specific mass markers could revolutionise the mapping of biochemical species in cells and tissues.   
+
#*There are several labs developing imaging using mass spectrometry where isotopic analysis is used to reveal the chemical makeup of biomedical systems. Full development of mass spectrometric imaging (MSI), to include labeled probes labeled with specific mass markers could revolutionise the mapping of biochemical species in cells and tissues.   
-
##Next generation microscopy, for instance Light sheet microscopy and super-resolution techniques such as Structural Illumination microscopy, Single Molecular Localisation Microscopy (e.g. PALM, STORM, GSDIM) and Stimulated Emission Depletion microscopy technologies are prime areas for new developments that probably can only be achieved by alignment between the life and physical sciences. In many respects these tools are in early stages of development for application in biomedical research. The technologies are considerably slower, more cumbersome, lack good probes and analytical tools. Better detectors, light sources and methods that can be implemented to image living cells, tissues and organisms are needed. In addition development of correlative methodologies to utilise two or more imaging technologies, in particular electron and atomic force microscopy with other light based modalities requires considerable development. Marrying these techniques up would yield valuable new data however only close development across physical and life science disciplines can allow for breakthroughs in these area.
+
#*Next generation microscopy, for instance Light sheet microscopy and super-resolution techniques such as Structural Illumination microscopy, Single Molecular Localisation Microscopy (e.g. PALM, STORM, GSDIM) and Stimulated Emission Depletion microscopy technologies are prime areas for new developments that probably can only be achieved by alignment between the life and physical sciences. In many respects these tools are in early stages of development for application in biomedical research. The technologies are considerably slower, more cumbersome, lack good probes and analytical tools. Better detectors, light sources and methods that can be implemented to image living cells, tissues and organisms are needed. In addition development of correlative methodologies to utilise two or more imaging technologies, in particular electron and atomic force microscopy with other light based modalities requires considerable development. Marrying these techniques up would yield valuable new data however only close development across physical and life science disciplines can allow for breakthroughs in these area.
#Data Management, Analysis and Visualisation.  All of these trends move towards creating larger and much more complex datasets. The computational requirements for handling the data created by genomic, proteomic and imaging studies is growing rapidly, and most estimates indicate that data volumes and the need for data processing will exceed the computational and storage capacities available [Nature,498,2013]. A critical need in the life and biomedical sciences is the delivery of new data compression technologies, data management systems, analytic and processing methods and tools, and complexity reduction algorithms that work at large scales to deliver the most optimal results that enable new discoveries, diagnostics and therapies.  
#Data Management, Analysis and Visualisation.  All of these trends move towards creating larger and much more complex datasets. The computational requirements for handling the data created by genomic, proteomic and imaging studies is growing rapidly, and most estimates indicate that data volumes and the need for data processing will exceed the computational and storage capacities available [Nature,498,2013]. A critical need in the life and biomedical sciences is the delivery of new data compression technologies, data management systems, analytic and processing methods and tools, and complexity reduction algorithms that work at large scales to deliver the most optimal results that enable new discoveries, diagnostics and therapies.  

Revision as of 20:11, 27 March 2015

Contents

Background

(This text is from the instructions. BioImagingUK has been asked to provide responses to this consultation.)

Building on our track record of working together to support interdisciplinary research across the physical, life and biomedical sciences, BBSRC, EPSRC and MRC are at an early stage in scoping a joint strategy to foster more diverse, fundamental, interdisciplinary technology development research. This is a new theme provisionally titled ‘Technology Touching Life’ (TTL). As part of the initial scoping exercise this consultation is being sent to universities/institutes, individual researchers, learned society contacts and industry representatives to garner views from the scientific community in order to inform the development of the TTL theme.

Discussions on TTL across the three Research Councils were initially stimulated by the EPSRC report The importance of engineering and physical sciences research to health and life sciences, published in May 2014. Fundamental breakthroughs in the life and biomedical sciences are often based on new physical science-based research technologies, which in turn often open up longer term opportunities for the economy and society. The TTL strategy aims to stimulate and support interdisciplinary collaborations to explore novel technologies and approaches that address application-driven challenges. By enabling joint working and two-way flow of ideas between life scientists and engineers/physical scientists we expect that TTL will ensure the UK leads future waves of foundational technology discovery for the life and biomedical sciences, and create new opportunities for commercial development.

Questions and Draft Answers

Within the broad scope of Technology Touching Life:

Q1. What are the ‘sweet spot’ areas where there is high potential for closer alignment across physical sciences and life sciences to lead to major advances?

There are literally dozens of opportunities across the life and biomedical sciences where a close alignment with the physical sciences could lead to major advances and discoveries. Three of the most pressing opportunities involve genomics and proteomics, imaging and the data sciences.

  1. In genomics and proteomics, we are on the cusp of a revolution. With critical advances in DNA sequencing and proteomic technology, most individual humans, domesticated animals and will soon their genomes sequenced, and their gene expression and protein abundance and modifications profiles mapped and know. The impact of having, for example, the gene expression and protein abundance profile of many different tissues in an organism, the different parts of a tumour, or the full lifecycle of an important food source can only be dimly imagined. It is very likely that this data when combined with other information (as described below) can lead to many important fundamental discoveries, diagnostics, and new therapeutic approaches for many modern diseases. Personal DNA sequencing is potentially a quite lucrative commercial market as well and the availability of affordbable genome sequencing will open up a large number of commercial opportunities. The resources to fund the development of new gene sequencing and protein profiling technology, which will require innovations in chemistry, engineering and data analysis should be considered a major strategic scientific, social and commercial priority. This will make good on the promise of this revolution and ensure the UK is a prominent player on the world stage in these domains.
  2. Imaging delivers measures the molecular and structural composition of biological and biomedical entities. Most importantly, many imaging modalities are capable of measurements in space and time. Imaging systems that provide spatio-temporal map, when combined with spectroscopic capabilities that reveal probe environment allows different components using a variety of spectral and or probe technologies means that it is now routine to probe the molecular and structural makeup and dynamics of biological systems. In the future by combining the physical and life and biomedical sciences we can foresee the development of new imaging modalities where most of texture combined with the spatio-temporal resolution to reveal chemical physical composition and dynamics that have to date not been available. Overall, imaging technology in the 21st century depends on the combination of development of new probes for revealing molecular and structural composition and new detection modalities for revealing the composition of biomedical systems. Some examples of imaging "sweetspots":
    • There are several labs developing imaging using mass spectrometry where isotopic analysis is used to reveal the chemical makeup of biomedical systems. Full development of mass spectrometric imaging (MSI), to include labeled probes labeled with specific mass markers could revolutionise the mapping of biochemical species in cells and tissues.
    • Next generation microscopy, for instance Light sheet microscopy and super-resolution techniques such as Structural Illumination microscopy, Single Molecular Localisation Microscopy (e.g. PALM, STORM, GSDIM) and Stimulated Emission Depletion microscopy technologies are prime areas for new developments that probably can only be achieved by alignment between the life and physical sciences. In many respects these tools are in early stages of development for application in biomedical research. The technologies are considerably slower, more cumbersome, lack good probes and analytical tools. Better detectors, light sources and methods that can be implemented to image living cells, tissues and organisms are needed. In addition development of correlative methodologies to utilise two or more imaging technologies, in particular electron and atomic force microscopy with other light based modalities requires considerable development. Marrying these techniques up would yield valuable new data however only close development across physical and life science disciplines can allow for breakthroughs in these area.
  3. Data Management, Analysis and Visualisation. All of these trends move towards creating larger and much more complex datasets. The computational requirements for handling the data created by genomic, proteomic and imaging studies is growing rapidly, and most estimates indicate that data volumes and the need for data processing will exceed the computational and storage capacities available [Nature,498,2013]. A critical need in the life and biomedical sciences is the delivery of new data compression technologies, data management systems, analytic and processing methods and tools, and complexity reduction algorithms that work at large scales to deliver the most optimal results that enable new discoveries, diagnostics and therapies.

These are the most obvious big wins for combining efforts in the physical and life sciences. Many of the most important outcomes of these developments can’t yet be imagined. Application of new technology inevitably reveals opportunities and knowledge that was simply unimaginable before its development. One example is the scale and importance of the microbiome in humans and animals and the interaction of an individual animal or plant with its own microbiome. It is nonetheless critical to invest in the development of these technologies so that the UK can benefit from the scientific, social and economic benefits they will create.

Q2. What trends or developments in engineering and physical science technologies are already emerging which you think will have impact in the life and biomedical sciences?

There are several ongoing major efforts in the physical sciences that will have massive impacts in the life and biomedical sciences across research discovery diagnostics and therapeutics. Some major points that we foresee will be extremely important:

  1. Efforts across the range of photonics to make increasingly smaller, brighter, and cheaper light sources should translate into research, diagnostic, and therapeutic tools that have a wide range of applications.
  2. The development of new probes for measuring chemical and structural composition and environment in living tissues and organisms is proceeding and will be an important part of future the development of new discoveries and diagnostics. Moving forward the development of multi-modal imaging probes where complementary imaging modalities can be used to reveal the biological and biomedical structure and dynamics will be incredibly important for revealing the molecular basis of disease and the effect of candidate drugs on these diseases.
  3. Nanotech, in particular small engineered materials, which are useful for delivering medicines to specific locations or under specific conditions should be an extremely powerful technology that will deliver benefit for society and science.
  4. A huge opportunity for the development of computational methods and technologies for managing, processing, analyzing and understanding the very large, heterogeneous ("big data") datasets acquired across all domains of the life and biomedical sciences will be fundamental for delivering the promise of stratified medicine and healthcare.

"The cultural baggage of biology that privileges data generation over all other forms of science is holding us back" [Nature,498,2013]

Q3. What important areas in the life and biomedical sciences are currently limited by existing technologies and require new technology developments to ‘unlock’ discovery opportunities and deliver a 'step change' in understanding?

Across all life and biomedical sciences there is a common challenge for handling sharing processing publishing and delivering knowledge from the large complex multidimensional, heterogeneous datasets that are now routinely collected in the life and biomedical sciences. This challenge has appeared because of the great advances in automation and detection in genomics, proteomics, imaging, and other quantitative modalities. As important as these technologies are, the computational methods and tools for handling these datasets has not kept up. This challenge occurs in all domains of the life and biomedical sciences. Dedicating resources for computational methods and tools is a critically important opportunity for investment and collaboration across the physical and life sciences.

Q4. What do you see as the key features of successful models of close working between physical sciences and life sciences in fundamental discovery research? Please use specific examples, national or international, where possible. You views on unsuccessful as well as successful models are welcome.

The current drive to interdisciplinary science is laudable and correctly recognizes the need to bring expertise from many different domains together to achieve substantial strategic goals that are important for science society and wealth generation. However the career and recognition models commonly in these projects derive from the now outdated need for an individual scientist to prove his or her own success for career progression, recognition and reward. While it is possible to bring scientists from different domains with different recognition and career progression mechanisms together, merely pretending these will combine and easily meld together is naive.

There are examples where true cross-disciplinary collaboration has occurred but the normal academic career progression has been discarded. One notable positive example is the Allen Brain Institute in Seattle where engineers, biologists, and informaticians have collaborated to build (over a 15 year timescale, a timeline that stretches long past conventional project horizons) the Allen Brain Atlas, a resource that now is becoming the foundation for the development of new scientific discoveries in neuroscience. One notable aspect of the Allen's work is that career progression and success for the Allen Insititute’s scientists are solely based on their contribution to the Allen Brain Institute’s mission and not their individual publication record, citation statistics, etc. Thus they are measured based on their contribution to the interdisciplinary project, not what part of the project they have somehow retained or branded for themselves. One message from this story is that large interdisciplinary teams that retain a focus on individual success may not be able to achieve the scale of accomplishment, discovery and contribution they might otherwise simply because the individual team members have to focus on their own progression and success.

Q5. What structures, activities and mechanisms help establish a culture of interdisciplinary research and strong interdisciplinary leadership in universities, institutes and centres?

Academic Consortia. The best and most effective way to establish a culture of interdisciplinary research is to promote the formation of active research-driven consortia that are formed by PIs and other researchers to address or develop research programmes and proposals that respond to a specific opportunity. Strategic opportunities can be driven either by universities of Research Councils with pump priming funding or strategic calls. Different scales can be used to drive the formation of interdisciplinary consortia in different domains or in domains with different levels of challenges. The specifications for these consortia should be relatively loose: a specific formula for proportions or types of biologists, physicists, chemists, engineers and/or computer scientists is usually too prescriptive to allow the research-driven definition of a well-constructed team focussed on a specific problem. Strategic research council funding initiatives can prime the pump for the development of these consortia especially if they include directives for building interdisciplinary teams. Good examples are the Next Generation Optical Microscopy call and the UK Regenerative Medicine Platform.

In 2015, there are now several examples of interdisciplinary consortia operating at and across UK universities. These operate using many different models, but a common theme is the linking of scientific activities and disciplines enables opens the doors to scientific and funding opportunities that aren’t available otherwise. In this sense, UK scientists have already formed interdisciplinary consortia across several themes and are ready to respond to the funding opportunities presented by the Research Councils.

Careers. At the level of the university there must be mechanisms to recognize the commitment of research time to interdisciplinary programs that stretch the conventional research portfolio within each department. If a physicist collaborates with a life scientist and the ultimate output is a paper in a biomedical journal then the credit for the physicist who appears as a middle author on the paper must be considered in his or her home department.

Industrial Partnerships. There are huge opportunities for linking academic and industrial efforts across the life sciences, biomedical research, engineering and physical sciences. Examples include the commercialisation of high throughput sequencing (http://www.illumina.com/technology/next-generation-sequencing/solexa-technology.html) and efforts to solve the computational challenges in personalized medicine (http://www.intel.com/content/www/us/en/healthcare-it/collaborations/ohsu.html). These partnerships are usually formed at the University or project level.

Q6. Please comment of the role that effective and inspirational leadership plays, giving examples where possible.

A critical component of interdisciplinary projects is strong leadership and management. Ensuring that all partners in an extended collaboration are interacting as necessary, delivering on promised tasks and committed to the promised timelines milestones and goals is an absolute necessity. In addition, there must be a respect of the needs of different project members, whose career goals (clinical progress, academic tenure, commercial success) will often not overlap.

Defining ‘inspirational’ leadership is difficult. The most inspirational leadership sometimes comes from supremely competent managers-- the inspiration comes from the consortium and collaboration delivering its scientific and strategic goals. Laissez-faire management is often a major reason why strategic projects fail.


Q7. How might the Research Councils working with research organisations (e.g. universities and institutes), industry and other stakeholders help address the issues raised in response to the questions above? Please provide examples of successful approaches (both national and international) where applicable.

The first priority in considering strategic options for driving interdisciplinary science is must be the science and technology development itself. The funding and delivery of the best and most important advances in science, diagnostics and therapy must be the overriding goal. Collaborations between the physical and life sciences are then a means to achieve this.

Academics are generally very good at bring together teams when the correct challenge is set. They can act as the glue between clinic, research and industry and thus enabling such people to bring together and then apply for funding, which may have many traditional funding routes (eg MRC, NHS, EPSRC, Innovate UK) in one go is important. This might be based upon an initial pure research project with then a seamless transmission to application and commercialisation (TSB, Innovate UK). This progression will always be challenging, but several funding mechanisms target specific parts of these steps (e.g., Pathfinder and several TSB schemes).

One of the challenges in delivering these collaborations and thus their potential scientific output and impact is developing the productive collaborations in the first place. Building bridges between different disciplines and establishing strong, strategic collaborations takes time and resources. It is therefore worth considering funding interdisciplinary collaborations at different levels. Shorter term proof-of-concept projects should be separated and funded separately from longer-term strategic efforts. The research councils aligned with universities, potentially using similar mechanisms as the MRC Confidence in Concept schemes could deliver these tiered funding lines.

Q8. Finally, we would welcome any other comments you have on developing the 'Technology Touching Life' theme.

TODO

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