The diversification and activity of hAT transposons in Musa genomes

Musa hAT element organization, abundance and phylogeny. Menzel et al. Chromosome Research 2015

Musa hAT element organization, abundance and phylogeny. Menzel et al. Chromosome Research 2014

Menzel G, Heitkam T, Seibt KM, Nouroz F, Müller-Stoerme M, Heslop-Harrison JS, Schmidt T. 2014. The diversification and activity of hAT transposons in Musa genomes. Chromosome Research 22: 559–571. DOI 10.1007/s10577-014-9445-5 and Pubmed link ID: 25377178 And author print hATs in Musa _2014_CR_MenzelEtAlAuthorVersion2014.

Sequencing of plant genomes often identified the hAT superfamily as largest group of DNA transposons. Nevertheless, detailed information on the diversity, abundance and chromosomal localization of plant hAT families are rare. By in silico analyses of the reference genome assembly and BAC sequences, respectively, we performed the classification and molecular characterization of hAT transposon families in Musa acuminata. Musa hAT transposons are organized in three families MuhAT I, MuhAT II and MuhAT III. In total, 70 complete autonomous elements of the MuhAT I and MuhAT II families were detected, while no autonomous MuhAT III transposons were found. Based on the terminal inverted repeat (TIR)-specific sequence information of the autonomous transposons, 1722 MuhAT I- and MuhAT II-specific miniature inverted repeat transposable elements (MuhMITEs) were identified. Autonomous MuhAT I and MuhAT II elements are moderately abundant in the sections of the genus Musa, while the corresponding MITEs exhibit an amplification in Musa genomes. By fluorescent in situ hybridization, autonomous MuhAT transposons as well as MuhMITEs were localized in subtelomeric, most likely gene-rich regions of M. acuminata chromosomes. A comparison of homoeologous regions of M. acuminata and Musa balbisiana BACs revealed the species-specific mobility of MuhMITEs. In particular, the activity of MuhMITEs II showing transduplications of genomic sequences might indicate the presence of active MuhAT transposons, thus suggesting a potential role of MuhMITEs as modulators of genome evolution of Musa.

Keywords Musa acuminata, Musa balbisiana, genome assembly, BAC, hAT transposons, FISH

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The damaging bureaucracy of academic peer preview

  • 309. Braben DW, Allen JF, Amos W, Ball R, Birkhead T, Cameron P, Cogdell R, Colquhoun D, Dowler R, Engle I, Fernández-Armesto F, Fitzgerald D, Hall J, Heslop-Harrison P. Herschbach D, Kimble HJ, Kroto H, Ladyman J, Lawrence P, MacIntyre A, Mattick J, Pelloni B, Randall D, Ray D, Roberts RJ, Seddon K, Self C, Swinney H, Vita-Finzi C. 2014. Peer preview tyranny: The damaging bureaucracy of academic peer preview. Letters. The Daily Telegraph 3 June 2014; p 21. http://www.telegraph.co.uk/comment/letters/10870609/The-damaging-bureaucracy-of-academic-peer-preview.html; commentary at http://www.telegraph.co.uk/science/science-news/10870995/Nobel-winners-say-scientific-discovery-virtually-impossible-due-to-funding-bureaucracy.html
  • SIR – Under current policies, academic researchers must submit their proposals to a small group of their closest competitors – their peers – for consideration before they might be funded. Peers selected by funding agencies are usually allowed to deliver their verdicts anonymously. They assess the proposal’s suitability for funding, whether it would be the best possible use of the resources requested, and determine, if it were successful, the probability that it might contribute to the national economy in some way. If the answers are satisfactory the proposal has roughly a 25 per cent chance of being funded. Peer preview is now virtually unavoidable and its bureaucratic, protracted procedures are repeated for every change in direction or new phase of experimentation or for whatever an applicant might subsequently propose. Consequently, support for research that might lead to major new scientific discoveries is virtually forbidden nowadays, and science is in serious danger of stagnating. Many scientists privately deplore these policies but their professional standing often depends on their acquiescence – a catch-22 that effectively diminishes public opposition to the policies. We call upon funding agencies to support sustained, open-ended research in unfashionable fields.
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Needs for understanding water and food security

Tube wells using water from deep aquifers for irrigation. How can the water be used most efficiently? Are the aquifers being depleted?

Tube wells using water from deep aquifers for irrigation. How can the water be used most efficiently? Are the aquifers being depleted?

“The earth’s land surface receives about 110,000 km3 of rainfall annually. More than half of this water is evapotranspired (transmitted from soils and through plants to the air); about 20,000 km3 falls on land that is cultivated in some form; and about 40,000 km3 becomes available in dams, lakes, rivers, streams and aquifers for human and environmental uses”

I make three critical recommendations for Water and Food Security: a robust, global measurement framework for water; a major genetic research effort related to crop water usage; and education at all levels that is critical to future agricultural sustainability

The water figures above come from the Food and Agricultural Organization of the United Nations Committee on World Food Security – High Level Panel of Experts on Food Security and Nutrition who were commissioned to prepare a report on Water and Food Security. [Guess the organizations who like acronymys: FAO UN WFS (and WFS with a different W) HLPE FSN all appear on the web!] The draft report makes some science-based contribution to the facts and defining needs for water usage and its availability with respect to food security, but in many areas is off-topic and does not cover the ground in relation to the request of the UN Committee on Food Security. People have been invited to comment on the report, and here I am giving my comments and response. I have significant reservations about the impact of the report in the present format.

At a little over 100 pages, it is far from concise, and is poorly structured, so data, recommendations and the key messages are lost. Unfortunately, I think the draft report also misses key aspects where robust scientific advice is needed to inform political, policy and treaty decisions or recommendations. Although indicated in the Terms of Reference, the target audience and route to implementation of recommendations should be made explicit and the report needs focus. I think that many areas of the third chapter, ‘Governing water for FSN’, stray into political issues, when the purpose of this report (and the Terms of Reference) is to provide scientific underpinning for robust policy advice.

In particular, I think there are three critical recommendations required in terms of Water and Food Security.
First, a robust, global measurement framework to collect data a world-wide map with high spatial and temporal (seasonal) resolution is required for water availability, usage and quality, throughout the world. This will inform policy decisions and give a base-line for interventions.
Second, a major genetic research effort is required to understand the genetic variation available within current and candidate agricultural plants, and to an extent animals (including fish and insects), as related to the efficiency of water usage; and to study how this variation can be exploited in current and prospective socioeconomic and farming conditions.

Trude Schwarzacher and HK Chaudhary discuss field selections and trials with students

Trude Schwarzacher and HK Chaudhary discuss field selections and trials with students

Thirdly, education is critical to future agricultural sustainability, ecological management, capacity building and equality. This recommendation should cut across other issues, and is important at all levels from primary school through to post-graduate and farmers.
While I am critical of the excessive length of the report, with discourses on management of somewhat peripheral water-related issues, I believe it does not give enough emphasis to the significant successful (or unsuccessful, and including reactive interventions to water problems) examples where science-based policy changes and management, implemented by farmers and regional governments, have occurred with respect to water and food security (including sustainable usage) usage in many countries over the last century.
– The significant Australian successes are not well covered – they go far beyond the water reform legislation in 2007- 2008; water management has become central in every family farm in that country (many of thousands of hectares) in the last two decades.
– Going further back, the remediation of arguably the greatest human-caused environmental catastrophe, in the 1930s, of the dust-bowls of the Western US, was an example of successful agricultural and water management reacting to a major problem.
– Within this century, two significant new policies are already having major effects on agricultural water usage as well as current and future, The Kingdom of Saudi Arabia has implemented major structural and regulatory changes, away from the plan for high production of cereals (self-sufficiency, as initiated in the 1980s) because it became clear in the 2000s that it is too resource-intensive in terms of water: trade with countries with more water is more efficient and sustainable for cereals. In the Indian Punjab, region-wide changes in agriculture now mean double cropping of much land, but depletion of aquifers was becoming a major possibility; restrictions on irrigation dates are now implemented.

It is good that the report considers the entirety of the position of water in food security and socioeconomic context. However, it is grossly imbalanced: the term ‘sanitation’ is mentioned no less than 133 times, more than twice ‘drink’… or ‘indust’…, or four times ‘salin’…! This is but one example where peripheral issues have high prominence, and I think that major rebalancing is required to focus on key issues. As another example where key issues are buried, the global population change is mentioned multiple times (2050 and two billion more people and increase in meat and oil consumption), the global figure means little compared to the impact in individual countries. For example, on page 16, the graph should show population growth for Ethiopia as well as other lines: the progress from famine of 1984 to a reasonably fed population now, with growth from 40 million to 96 million in the same period, is remarkable.

With respect to my three aims set out above,
GLOBAL MEASUREMENT FRAMEWORK
I believe it is important that all countries have a rigorous measurement framework for the status of water with a national, high resolution grid, and finer resolution in the vicinity of open water or aquifers (coasts, lakes or major rivers). The appropriate grid scale and parameters must be defined in conjunction with timescales and resource implications, but my suggestion would be 10km over most areas and 1km in water-impacted regions. There should, though, be robust, evidence-based reasons regarding grid size and where a larger grid is appropriate, as it will be in landscapes with even geology, vegetation and unchanging features. The measurements should include water input, flows/extraction, evapotranspiration, groundwater, water tables, salinity, and BOD among other routine parameters. Page 9 notes “In water, data is very often a challenge for action. Data definition, quality and transparency, precision at lower geographical scales, disaggregation by users, and gaps are the biggest issues.” but there is little mention later of the need for international data. Section 8 also has some relevant material.
How will this be implemented? The single mention of “remote sensing” on p79 is extremely weak: it is a key technology for assessment and monitoring of water amounts, distribution, quality and flow; policy definition, development and research on new water usage approaches, even for plant breeding selection approaches. Is it satellite, aircraft, ROV, in situ transponders/sondes? The one mention of remote sensing in the draft report is even in the context of “citizen science” – I would suggest data collection on water is a major duty of every government (as, indeed, it has been up to now) and remote sensing is undoubtably the way to improve the quality and granularity of water data for use by national governments, geographical regions, and international organizations.

As pointed out, water availability is highly variable across time and space and characterised by the complex interactions. Other key methods are isotope analysis with environmental isotopes to assess water resources, recharge of aquifers, nutrient flow an

Irrigated cereal plots in the Persian Gulf

Irrigated cereal plots in the Persian Gulf using groundwater from surrounding mountains

d other aspects of monitoring of water and aquifers: training and standardization of these methods is required. There are problems with current published statistics including quality, granularity, comparison/standardization of types.

GENETICS RESEARCH
It is remarkable that no mention of different crops and plant breeding opportunities except as “Seed multiplication/drought resistant seeds” and “Crop genetic improvement programme/Animal genetic resources/ Genetic improvements can lead to crops that required less water or are more drought resistant” as a vague reference in a table at the very end (p. 101). Such research is critical to the sustainable intensification of agriculture, and the increase of appropriate, rain-fed or ground-water based, agricultural production systems to feed people without overuse of water resources. Plant breeders and research scientists recognize not only that there are huge differences between difference crop species in water use and water quality requirements, but there is also extensive genetic variation within existing crop species and their wild relatives. With more research, the genetics can be discovered and applied to ensuring productive agriculture while using less water.

Ensete trails - Ethiopian banana - trials with PHH and  Bizuayoue Tesdaye. An important crop for food security in drought years

Ensete – Ethiopian banana – trials with PHH and Bizuayoue Tesdaye. An important crop for food security in drought years

There is also need to consider nutritional aims in the breeding context – of both the plants (beyond water requirements), with respect to nitrogen and other nutrients; and importantly with respect to the nutritional value of the crops, the major impactor on human health.
The genetic needs should be in the context of existing programmes but not exclude potential significant contributors: CGIAR Centres, the Joint IAEA/FAO Genetics and Plant Breeding programme, national agricultural research centers (NARs), Universities and the private sector.

EDUCATION
A key to ‘Water and Food Security’ is education. There is minimal mention in the report of this aspect beyond a phrase “how to provide small farmers in particular with the necessary information to improve productivity, access to markets etc. In this process, the use of open source software should be the basis of all developments in this field”. Why the limitation to small farmers? Why open source? The private sector has an excellent track record in delivery of products to farmers and teaching them how to use them. Indeed, heavily protected technology such as mobile phones, internal combustion engines, personal computers, or even (unnecessary) soft and alcoholic drinks, have the widest market penetration even when ‘open-source’ equivalents exist. (In the context of open-ness, much more of a problem is that Governments keep publicly-funded data of water use and quality secret.)
The use of water for efficient agriculture starts with the farmer, and it is critical that farmers are given access to up-to-date research and demonstrations of best-practices in water-efficient agriculture. They are the people – female and male – who will make the difference to agricultural water usage and ensure food sustainability. Broader education occurs through early-adopters with demonstration technology, University and NAR outreach centres staffed with people trained to undergraduate or Masters-level. In much of South India for example, the benefits of large numbers of such people are clear in the disease-control and agronomy practices which are now universal. Involvement of communities at all levels, from use of questionnaires through to community partnerships or cooperatives, can deliver sustainable water usage.

Beyond the farmer-level, University research with appropriately trained biologists, agronomists, and geographers is critical to understand the role of water in the environment and food security. Political interference has no part in this science-based training, and there have been problems in implementing and establishing fundamental aspects of agricultural developments. The implementation requires high level governmental support with appropriate funding; international collaborations as the way to develop the new technologies required now and in the next 100 years.

CONCLUSIONS
Unfortunately, I feel that the current Draft report is too vague and does not address key issues in a way that has an implementation pathway. No doubt that major interventions are required to increase the sustainability of use of the world’s water, with efficient usage and increased production from agriculture. This can be achieved by measuring water usage, improving the genetics of crops, and teaching people. The policy questions need to be well defined, and lead to high quality and robust scientific advice feeding into those policy questions.

Professor J.S. (Pat) Heslop-Harrison November 2014
Department of Biology
University of Leicester
Leicester LE1 7RH UK
E-mail: phh4@le.ac.uk Skype: Pat.HH Twitter: PatHH1
Websites: http://www.molcyt.com http://www.sblab.org
Phone: +44/0 116 252 5079 / 3381 FAX: +44/0 116 252 2791

 

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Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene

Convergent Evolution in Macaque and human - Ottolini et al. 2014

Convergent Evolution in Macaque and human – Ottolini et al. 2014

Ottolini B, Hornsby MJ, Abujaber R, Macarthur JA, Badge RM, Schwarzacher T, Albertson DG, Bevins CL, Solnick JV, Hollox EJ. 2014. Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene. Genome Biol Evol. 2014 Oct 27. pii: evu236. [Epub ahead of print] http://gbe.oxfordjournals.org/content/early/2014/10/26/gbe.evu236.long

β-defensins are a family of important peptides of innate immunity, involved in host defense, immunomodulation, reproduction and pigmentation. Genes encoding β-defensins show evidence of birth-and-death evolution, adaptation by amino acid sequence changes and extensive copy number variation (CNV) within humans and other species. The role of CNV in the adaptation of β-defensins to new functions remains unclear, as does the adaptive role of copy number variation in general. Here, we fine-map CNV of a cluster of β-defensins in humans and rhesus macaques. Remarkably, we found that the structure of the CNV is different between primates, with distinct mutational origins and CNV boundaries defined by retroviral long terminal repeat elements. While the human β-defensin CNV region is 322 kb and encompasses several genes, including β-defensins, a long non-coding RNA gene and testes-specific zinc-finger transcription factors, the orthologous region in the rhesus macaque shows CNV of a 20 kb region, containing only a single gene, the orthologue of the human β-defensin-2 gene. Despite its independent origins, the range of gene copy numbers in the rhesus macaque is similar to humans. In addition, the rhesus macaque gene has been subject to divergent positive selection at the amino acid level following its initial duplication event between 3 and 9.5 million years ago, suggesting adaptation of this gene as the macaque successfully colonised novel environments outside Africa. Therefore, the molecular phenotype of β-defensin-2 copy number variation has undergone convergent evolution, and this gene shows evidence of adaptation at the amino acid level in both primates.

Ottolini B, Hornsby MJ, Abujaber R, Macarthur JA, Badge RM, Schwarzacher T, Albertson DG, Bevins CL, Solnick JV, Hollox EJ. 2014. Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene. Genome Biol Evol. 2014 Oct 27. pii: evu236. [Epub ahead of print] http://gbe.oxfordjournals.org/content/early/2014/10/26/gbe.evu236.long

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Molecular cytogenetics research group October 2014

MolCytGroupSept2014_PHH7675bAt our lab. meeting a couple of weeks ago, we were happy to welcome two new PhD students to the group. Here we all are in the lobby of our Adrian Building. We are from six countries, and work on a diverse range of molecular cytogenetics projects.

From left to right, left of DNA molecule: Amal Alyamani (Wheat repetitive DNA), Ramesh Patel (Technical), Chetan Patokar (Wheat-Thinopyrum introgression), Rubar Salih (Taraxacum diversity), Pat Heslop-Harrison, Juceli Gouveia (Fish microsatellite organization) ; Sarbast Mustafa (Sheep and bovid satellite DNA diversity). Right of DNA molecule: Trude Schwarzacher, Jotyar Mohammed (Aubrieta biodiversity), Khaloud Alarjani (Brassica repetitive DNA), Stuart Desjardins (Fallopia/Knotweed relationships), Nauf Alsayid (Saffron and Crocus diversity), Fabiola Santos Carvalho (Brachiaria forage grass molecular cytogenetics; her picture is inserted). Adel Sepsi (Centromeres and epigenetics in wheat introgression lines).

Below are a series of pictures of the visit of the new President and Vice-Chancellor of the University of Leicester, Professor Boyle, in our laboratory. More information about this visit will follow.

DSC05335 DSC05334 DSC05333 DSC05332 DSC05351BoylePatHHTrudeSarbast
DSC05358 DSC05357 DSC05356 DSC05355 DSC05354 DSC05353 DSC05352 DSC05346 DSC05345 DSC05343 DSC05341 DSC05340 DSC05339 DSC05338 DSC05337

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Chromosomal evolution in Brachiaria forage grasses with Fabiola Carvalho Santos

Fabiola Santos overlooking Brachiaria trials in Brazil

Fabiola Santos overlooking Brachiaria trials in Brazil

Fabiola Santos from University of Londrina, Brazil, is working on the Chromosomal evolution and the organization of repetitive DNA sequences in diploid and polyploid Brachiaria forage grasses in the molecular cytogenetics group in LeicesterBrachiaria is most important cultivated forage grass genus in Brazil (with billion-dollar production), and the genus includes diploid and polyploid species with similar and small chromosomes and basic numbers of x=6, x=7 and x=9. Many are apomictic and may multiply vegetatively. Fabiola is studying the genome structure and the monoploid complement to provide information about the origins of the polyploids and structure of the genome. In particular, using bioinformatic and molecular cytogenetic methods, she is exploiting rDNA, microsatellites, tandem repeats and transposable elements to characterize major genomic components, and to identify chromosomes by in situ hybridization. Questions include What is the monoploid complement – x number – for Brachiara? What is the distribution of retroelements and microsatellites across the genomes? Can we develop probes that allow identification of many individual genomes and chromosome types – with either localized probes or whole-chromosome paints?

Brachiaria bryzantha chromosomes (2n=4x=36) stained  blue with DAPI and showing some chromosomes with less labelling with a retroelement probe.

Brachiaria bryzantha chromosomes (2n=4x=36) stained blue with DAPI and showing some chromosomes with less labelling with a retroelement probe.

As well as developing karyotypes and understanding processes of genome evolution and speciation, the results will assist breeders in characterization of interspecific hybrids.

Her preliminary results are presented at the Plant Molecular Cytogenetics in Genomic and Postgenomic Era Conference in Katowice, Poland, in September 2014 in a poster by Fabíola Carvalho Santos, André Luiz Laforga Vanzela, Trude Schwarzacher and Pat Heslop-Harrison.

Fabiola is based in the Department of Biology Science, University of Londrina, Londrina, PR, Brazil. email: fabiolacs1786(a)gmail(dot)com

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George Fraser (1955-2014) Professor of Detector Physics and his biology

Professor George Fraser (1955-2014)

Professor George Fraser (1955-2014)

My colleagues and I were devastated by the news of the untimely death of our collaborator and friend George Fraser (22 July 1955 — 18 March 2014). George had a unique combination of vision of the applications of detector physics, knowledge from space research, optics, and electronics which is a huge loss to the whole research and imaging community. He was Professor of Detector Physics and Director of the Space Research Centre of the University of Leicester.

I had the privilege of working with George from soon after I joined the University in 2000. We were interested in spectral imaging and quantitative fluorescence microscopy. Within a short time of our first meeting, it was clear that the detectors he was working with for space applications could address the problems we were facing in microscope imaging. These included spectral imaging, to get away from the need to put filters or gratings in front of fundamentally monochromatic detectors, and the quantification of signal. Our discussions soon led to collaboration exploiting his knowledge of novel detector technology, and after proof-of-principle experiments with George at European Space Agency Technology Centre ESTEC, we wrote two manuscripts and a patent (linked below).

George and STJ drawings

George and STJ drawings

Moving beyond the preliminary experiments, it became clear there were additional advantages in huge signal-to-noise ratios, background rejection, and novel ways the detectors could be used with the additional dimension of photon arrival time.

Another strength of George soon became apparent in the wish to exploit the technology. In October 2004, we founded a company, BioAstral Limited, to develop the technology for a broad range of applications in biology. As we wrote, the STJ cryogenic detector is 1000 times more powerful at detecting fluorescence in biological assays than current technology, and it is unique in giving the colours of photons arriving without resort to filters, gratings or other spectroscopy.

George Fraser, Pat Heslop-Harrison, Andrew Holland and Trude Schwarzacher - Inventors on the STJ patent

George Fraser, Pat Heslop-Harrison, Andrew Holland and Trude Schwarzacher – Inventors on the STJs in biology patent

George had amazingly broad interests and unique insight into applications of his research, in technical and commercial terms – he really knew what ‘impact’ was. As such, he was looking for ways that Space science, and particularly his expertise in imaging, could be developed into a commercial product. At the time of his death, he was a Director of three commercial limited companies, BioAstral, Spectral ID and Gamma Technologies, as well as a Director of the National Space Centre’s NSSC Operations.

The cryostat/refrigerator/cooler for the optical STJ operating at 280mK in Leicester

The cryostat/refrigerator/cooler for the optical STJ operating at 280mK in Leicester

Developing the imaging technology where I was involved had formidable technical challenges with respect to obtaining the temperatures required for operation, building the electronics and engineering both the optical and electronic outputs, and George was up to continuous developments in this direction, towards having our own detector connected to a microscope in Leicester. Work he led ranged from getting the temperatures of a few hundred millikelvin without needing hundreds of litres of liquid helium, through to trapping of the earth’s magnetic field in the superconducting junctions and googlies like Oxford Instruments supplying US 120V equipment with UK 240V connectors which slowly blew up. Each one of challenges George could overcome with innovative solution, but sadly we never truely got beyond ‘first light’ in telescope terminology with the system in Leicester.

In other work in biology, George was able to use his insight in mathematical analysis of photon colour based on novel understanding of the optical properties of fluorochromes used in biology. This lead to some really interesting work and clearly could have been exploited for improved extraction of data from any multifluorescence assays used in biology. While there was substantial work involving a number of students, these ideas were only published in a patent (see below).

A huge regret in the work with George was that we never succeeded in obtaining any significant funding to develop the detector technology to the point it could be used routinely in biology. All our work was done with shoe-string funding, and we all were putting giant amounts of effort into writing applications and discussing the implications and applications, but it was all regarded as too early stage or too late stage.

I will miss my regular and wide ranging discussions with George on imaging and analysis. I remain in no doubt that cryogenic detectors have a major role in biology, as well as space science, in the future. Their development has been set back enormously by George’s sudden death. I hope that one of the many memorials to him will be the future widespread application and exploitation of STJs and TESs.

This in memoriam note is the basis of my overview of George’s work in biology for the memorial celebration held at the University of Leicester for George Fraser on 5th September 2014

Pat Heslop-Harrison. phh@molcyt.com http://www.molcyt.com

I have published two papers jointly with George over the years:
245. Fraser GW, Heslop-Harrison JS, Schwarzacher T, Verhoeve P, Peacock A, Smith SJ. 2006. Optical fluorescence of biological samples using STJs. Nuclear Instruments & Methods in Physics Research Section A-Accelerators Spectrometers Detectors and Associated Equipment 559(2): 782-784. doi:10.1016/j.nima.2005.12.136

226. Fraser GW, Heslop-Harrison JS, Schwarzacher T, Holland AD, Verhoeve P, Peacock A. 2003. Detection of multiple fluorescent labels using superconducting tunnel junction (STJ) detectors. Review of Scientific Instruments 74 (9): 4140-4144. DOI: 10.1063/1.1599059

Another paper was in an advanced draft at the time of George’s death:

Labelled cell images detected by an STJ array on a fluoresence microscope

Labelled cell images detected by an STJ array on a fluoresence microscope

G. Torricelli, Trude Schwarzacher, Peter Verhoeve, Didier Martin, J. S. (Pat) Heslop-Harrison, George W. Fraser et al. Hyperspectral imaging of biological samples using a superconducting tunnel junction (STJ) camera
We are now working to complete this work.

We have a patent issued for use of cryogenic detectors – either the fast-responding STJ superconducting tunnel junctions, or slower TES, transition edge sensors.

Fraser GW, Heslop-Harrison JS, Holland AD, Schwarzacher T (unordered) 2003. Detection of the energy of photons from biological assays. Patent. September 2001, published 20th March 2003 under publication number WO 03/0233 76, application number is PCT/GB02/04019

A second patent on the quantitative analysis of biological fluorochromes was also granted: Fluorescence labelling Fraser GW and Ray DJM. WO 2008081203 A2 “This invention generally relates to techniques for fluorescence labelling, and to methods, apparatus and computer program code for processing fluorescence signal data.”

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