Name

Professor J.E.Allen

Affiliation

University of Oxford

Address

Department of Engineering Science

University of Oxford

Parks Road

Oxford OX1 3PJ

Telephone

01865 273000

Fax

01865 273010

E-mail

john.allen.eng.ox.ac.uk

Brief summary of main points

   I wish to make a firm proposal that the United Kingdom should take part in the programme of research using the International Microgravity Plasma Facility (IMPF) to be installed on the International Space Station. The IMPF project began as a proposal to the European Space Agency (ESA) in 1999. This proposal was one of six to receive the highest rating in ESA's international peer review. As a result an International Advisory Board was formed whose duties, in the first place, were to make recommendations to the German Aerospace Centre (DLR). A feasibility study was then carried out by the German Company Kayser-Threde, funded by the DLR. Subsequently an International Announcement of Opportunity for Microgravity Research was made.

   I have been a member of the Advisory Board for the International Microgravity Plasma Facility (IMPF) since its inception. All the recommendations of this board are readily available on the web at <http:/www.microgravity.net>. I am also a member of an active European Network on Complex (Dusty) Plasmas; seven laboratories are engaged in this activity, in Germany, Norway, Italy, Portugal and the UK.

Further details and background

.Scientific and Technological Relevance

   The basic science in this project is that of the study of the behaviour of dust particles in a plasma. Such particles are somewhat like floating Langmuir probes in that no net current flows to them. In the steady state case the electron current and the ion current must therefore be equal, if secondary emission is negligible. The dust particle then acquires a negative charge, of the order of 10,000 electrons and a corresponding negative potential. The particles then interact with each other and can form "crystal-like" structures, or behave more like liquids or gases. The mixture of dust particles, ions and electrons is sometimes referred to as a "colloidal plasma". However the analogy cannot be carried too far, because the system is not in thermal equilibrium.

   The interaction between particles is not completely understood. Clearly there is a repulsive force, since they are all negatively charged (in the vast majority of cases).

Some experimental reports in the literature describe a screened Coulomb potential, but agreement has not yet been reached on the factors that determine the screening length. One of the difficulties here is that laboratory experiments have been carried out on the behaviour of dust particles in a space charge sheath. This is because the weight of the dust pulls the dust particles out from the plasma and into the adjacent sheath. These experiments are of considerable interest but experiments in the central plasma region are essential, which is the reason for devising experiments to be performed on the International Space Station, where gravitational effects are practically eliminated. The technological relevance relates largely, but not exclusively, to nanotechnology. As an example, microcrystals can be grown in plasma discharges in Silane or Methane and very interesting results have been obtained on the growth of microcrystalline silicon films at the Ecole Polytechnique in Paris. Techniques for manipulating particles are being developed, in a number of laboratories, which suggests the manufacture of some very interesting microelectronic devices. The first experiments on moving dust particles around in a plasma, using a low power laser beam, were in fact carried out in Oxford. Industrial aspects will be pursued by an IMPF team led by Professor G. Kroesen of the Eindhoven University of Technology in the Netherlands; their work includes particle growth, particle coating and the avoidance of the agglomeration of microcrystals. This is clearly long-term research, but is very likely to open up new areas of technology in ground-based industry.

   In general the research is of interest to three different communities: those working in space science, those working in technological plasmas and those working in basic plasma physics. In space science dust is important in interstellar clouds, comets, interplanetary dust, the magnetosphere, the ionosphere and planetary rings. Needless to say, plasma is ubiquitous, so the dust particles will become charged. Much of this dust is in regions where gravity is unimportant. The technological relevance has already been referred to. One can add that nowadays particles are grown in gas discharge plasmas for use as chemical catalysts and for compression into new materials with improved mechanical properties; such research has been carried out for some years at the Ecole Polytechnique de Lausanne, Switzerland. Turning to basic plasma physics, once dust is introduced into a plasma the whole subject needs to be re-examined ab initio. It must be remembered that we are not simply introducing additional heavy and highly charged ions into the system. The dust particles act as sinks for charged particles; one can add that the existing theoretical literature is largely unsatisfactory in this respect. One aspect of experiments with dust particles is that it they can be used for diagnostic purposes to determine electric field distributions in plasmas and sheaths.

Name

Prof. H. Oya Alpar

Affiliation

School of Pharmacy, University of London

Address

Centre for Drug Delivery Research

29 – 39 Brunswick Square

London WC1N 1AX

Telephone

020 7753 5928

Fax

020 7753 5942

E-mail

Oya.alpar@ams1.ulsop.ac.uk

Brief summary of main points

As a member of the ESA Topical Team, I would like to impress the importance of an active UK involvement in the ESA ELIPS (European Programme for Life and Physical Sciences) and the use of the International Space Station. Our project aims fall within that of improving health, and innovating technologies and processes, and I feel access to ISS and ESA support is essential to achieve our objectives. Together with this we should also form strong links with NASA to achieve synergy in intellectual advancement and health benefit.

Further details and background

Microsphere and microencapsulation technologies have found application in a range of industries, from pharmaceutical and biomedical to agrochemical and electronics. There are however, fundamental processes involved in the microencapsulation process for which a more detailed and mechanistic understanding is required. For example the interfacial phenomena occurring during solvent exchange at the solid/liquid and liquid/liquid interfaces, and the increased crystallinity of large polymer molecules. The microgravity environment of the ISS provides the ideal environment to isolate the different aspect of the microencapsulation process for a more comprehensive approach to the work.

Using a requisite multidisciplinary approach, elucidation of these mechanisms will provide a strong platform for further development of microsphere delivery systems for gene, vaccine and drug delivery, as well as biomedical diagnostic technologies.

In addition to the contribution to the advancement of science, and its implication on terrestrial health, there is also considerable commercial benefit to be gained by improving on microencapsulation technology.

Name

Dr LG Briarty

Affiliation

University of Nottingham (retired18 months ago)

Address

9 The Cloisters

Beeston

Nottingham

NG9 2FR

UK

Telephone

(44) (0) 115 9250 964

Fax

E-mail

lgbriarty@waitrose.com

Brief summary of main points

The UK does have a number of groups capable of and interested in

microgravity research, but the current research organisation and funding

climate mitigates against their taking up this interest.

Goodwill towards the UK from ESA in microgravity research has been

significant in the past as I can testify from my own experience as a PI on

various missions (Shuttle IML-1, two parabolic flights, Foton 12 mission).

This can't last much longer unless  we make some real investment in the

programme; the result of the UK's "wait and see approach" must  be a cooling

off and even antagonism towards UK useage of the ISS.

Throughout Europe the first generation of space-experienced researchers is

nearing retirement.  In most other countries a further generation is being

brought on and it is these who will understand and make use of the ISS as a

research facility.  This isn't the case in the UK and again we risk being

left out.

As well as being a research facility the ISS is a major stimulus to

international scientific collaboration.  It will result in new and expanded

research programmes from which the UK risks being left out.

Hope this helps

Greg Briarty

Further details and background

Name

Dr Rob Buckle

Affiliation

Medical Research Council

Address

20 Park Crescent

London W1B 1AL

Telephone

020 7636 5422

Fax

020 7670 5124

E-mail

robin.buckle@headoffice.mrc.ac.uk

Brief summary of main points

MRC has recently been examining its research strategy in relation to space-based biomedical research programmes, and to this end the MRC and BNSC recently hosted an international workshop to discuss this issue, and the benefits that such programmes might provide for terrestrial health needs.

The preliminary conclusion reached is that a strong case has not been made for making significant investments in this area, and MRC could not support the earmarking of funds for such research programmes unless this was additional to the current research budget.

More specifically:

·         While biomedical research in space is clearly needed to support the programmes of manned space flight, the main benefit of such research is to the health of astronauts, rather than to the health of the terrestrial population.

·         The UK has several pockets of excellent research in this area, although there is currently a lack of critical mass and co-ordination, and links to the broader biomedical community are weak. Nevertheless, some possibilities exist for improved interaction with those co-ordinating NASA and ESA-funded programmes.

·         Any decision to commit funding towards space research programmes should only be taken once a rigorous cost / benefit analysis has been undertaken.

Further details and background

The MRC and BNSC recently hosted a one-day workshop entitled ‘Space for health, or health for space?’ at the Royal Society in London on 5 August 2002. This workshop followed an earlier consultation exercise undertaken in 2001, during which the MRC asked both national and international scientists involved in microgravity research to advise on the scientific opportunities afforded by microgravity for research in cell biology and physiology. The workshop brought together 30 leading scientists from both the UK and overseas to discuss the opportunities presented by space-based research programmes in the area of biomedicine, and the benefits that such programmes might provide for terrestrial health needs. The meeting was structured to allow discussion of the role of space research in four areas of physiology – bone, muscle, cardiovascular and neuro-physiology.

The main aims of the workshop were:

·         To inform MRC’s research strategy in relation to biomedicine and space, given that research funded by MRC must ultimately address the health needs of the UK population and UK wealth creation.

·         To identify if there are unique opportunities afforded by research in space that might prove beneficial to terrestrial health.

·         To inform MRC’s and the other Research Council’s position on the value of “microgravity” as a platform / tool for research, and on potential UK participation in the ESA Life and Physical Sciences Programme (ELIPS)

·         To help assess the competitiveness of the UK in space biomedicine.

·         To identify how research activities linked to space programmes might be most effectively linked to the non-space scientific community.

·         To identify the opportunities and benefits of engaging more closely with ESA and NASA over the medium/longer term.

An expert advisory group was also present throughout the workshop, were asked to draw some conclusions and recommendations based upon the presentations and discussions of the workshop. This group met privately towards the end of the workshop and came to the following conclusions:

·         Biomedical research in space is clearly needed to support the programmes of manned space flight. The main benefit of such research is to the health of astronauts, rather than to the health of the terrestrial population.

·         While the UK has several pockets of excellent research in this area, there is currently a lack of critical mass and co-ordination, while links to the broader biomedical community are weak.

·         Microgravity provides an interesting tool with which to probe normal human physiology, although its relevance to pathophysiology needs to be more convincing.

·         Investigations into the loss of bone and muscle mass in conditions of microgravity may further our understanding of the basic mechanisms underlying the turnover of such tissue. However it has yet to be established whether this is a useful model in terms of understanding the processes of ageing.

·         The studies being performed in space offer some unique possibilities for the area of human physiology. For example, whole organism experiments can be performed in the human context, and dissociation studies are also possible. However the majority of important questions being posed could be tackled on earth by careful design.

·         Cardiovascular physiology represents an area of opportunity to further understand basic physiological processes, although space studies do not provide a good model for heart failure and other cardiovascular disease processes.

·         The area of neurovestibular research offers some possibilities, for example in relation to sensory-motor integration studies and cellular/molecular adaptation, although UK efforts in space research in this area are modest. Furthermore there are increasing terrestrial opportunities offered by virtual reality approaches

·         Current studies are generally descriptive, and the knowledge base at present is insufficient to ask the critical questions that microgravity might be able to uniquely answer.

·         The study population in space research is atypical, since astronauts are a highly selected group of fit and intelligent individuals.

·         The small numbers of astronauts that can be analysed gives rise to problems of statistical power in space research, and effort should be put into establishing new biostatistical methodology.

·         Space programmes may have a role for the development of bioinstrumentation, such as miniaturised imaging modalities; however the lack of statistical power in space studies will remain to be a problem

·         Due to its greater investment in manned space flight, NASA has a more significant biomedical research programme, and a larger physiological database, than ESA.

·         Any decision to commit funding towards space research programmes should only be taken once a rigorous cost / benefit analysis has been undertaken

·         The UK should establish better links between its biomedical researcher community and those involved in space research (through NASA and ESA). Opportunities exist for improving the design of the experiments performed in space, and UK experts could make valuable contributions in this area.

Name

Anthony MJ Bull

Affiliation

Imperial College London

Address

Department of Bioengineering

Imperial College

London SW7 2BX

Telephone

+44 20 7594 5186

Fax

+44 870 125 4985

E-mail

a.bull@imperial.ac.uk

Brief summary of main points

To quickly summarise my relevant research interest, it is chiefly in the field of movement analysis and the mechanics of joints in microgravity. I have some experience of microgravity research, undertaking flights with both ESA and with the Russians.

I and my colleagues would wish to be able to maintain and obtain extended access to parabolic flight programmes in the future. This work simply cannot be attempted without these experimental conditions.

If you wish to know a little more about the work, then do contact me.

Further details and background

Joint loading in microgravity: muscle optimisation of movement. Different muscular control strategies for movement. Applications of the work: devising different control strategies of bone loading - redistributing load on the joint, bone re-modelling (osteoporosis applications).

Name

Naomi Chayen

Affiliation

Imperial College London

Address

Biological Structure and Function Section,

Division of Biomedical Sciences,

Faculty of Medicine, Imperial College of Science,

Technology and Medicine,

London SW7 2AZ, U.K.

Telephone

020-75943240

Fax

020-75943169

E-mail

n.chayen@ic.ac.uk

Brief summary of main points

Why crystallise proteins?

Protein crystallisation has gained a strategic and commercial relevance in the post-Genomic era in which X-ray crystallography will play a major role. Current genome projects are expected to reveal numerous new targets for therapy of human disease.  However, it is usually not the genes themselves which are the targets, but the proteins encoded by them. The function of these proteins is determined by their three-dimensional structure and drugs can influence the function by precise atomic interactions with the protein. The most powerful technique for determining protein structure is X-ray crystallography, which is totally dependent on highly ordered crystals. Obtaining such crystals is the major bottleneck to structure determination. With the advent of Structural Genomics this problem is becoming increasingly acute giving rise to an urgent need for designing new and improved methods for producing high quality crystals. The demand for structures is not only in the medical sector but also in industries that utilise protein engineering for making a variety of  products (agricultural, washing powders, sugars and many other products).  It is often the case that crystals are produced, but they are not of good enough quality to undergo X-ray analysis. It is still not understood why some proteins (as well as other biological macromolecules) do crystallise with ease, while most refuse to produce suitable crystals. Better understanding of the fundamental principles of the crystallisation process will enable the design of new and improved methods for producing the desired crystals.

Current problems regarding crystallization in Space

The issue of crystallisation in Space is a controversial one due to conflicting results reported in the scientific literature.  A large number of scientific publications report that crystallisation of macromolecules in microgravity does indeed improve the quality of the crystals obtained. On the other hand, there are other reports opposing this claim, this is mailnly due to the fact that the success rate of protein crystallisation in Space has to date, only been 20%.  The reasons for this are only now beginning to emerge.  In recent years, experiments in micogravity are being conducted in a far more systematic way compared to previous experiments which were heavily reliant on luck. This is due to improved apparatus and awareness of the subject. With the aid of CCD video and other diagnostic tools it is now possible to monitor crystal growth in Space. As a result, researchers are beginning to realise the crucial factors on which to focus when conducting experiments in Space. (e.g. the importance of finding the optimal conditions in Space which may be totally different from the optimal conditions on Earth as well as the consequence of choosing the right method of crystallization).  A variety of apparatus made by NASA and The European Space Agency (ESA) for conducting both screening and diagnostic experiments in microgravity is now available using all methods of crystallization.

British Experiments

British scientists have set some bench marks and have influenced the way of conducting protein experiments in microG which others are following (e.g. highlighting of the work done by  Helliwell in Science (1995) 270, 1921; discontinuation of the vapour diffusion method by ESA based on the results of Chayen and Helliwell (1999) Nature 398, 20). Dr Skinner who was in Cambridge (but left for the USA) did an experiment in 1994 with a team of Europeans and Americans that showed improvement in diffraction of microG grown crystals. This experiment was not via ESA but using NASA apparatus. I have acted as Principal investigator on ESA, NASA and Russian missions, some in collaboration with other British scientists. Each of these misssions resulted in publications (listed in the next page) showing that microgravity has an effect, in most cases beneficial. Our experiments (all via ESA) have lead to new understanding of the process of crystal growth in microgravity which offer an explanation as to why in some cases the benefits were not full (Collaboration between Royal Holloway, Manchester and Imperial). I am currently designing new reactors for protein crystallisation is Space together with a German company working for ESA.

During the period of flying via ESA, We UK Scientists did the microG work without any support, really in our spare time, while the other Europeans received handsom funding form their National Agencies. But, at least we had the flight opportunities which are now at threat. Because the UK has been taken off the ESA missions, I am currently flying protein crystallisation experiments directly via NASA at their invitation, but one cannot be sure how long such a 'private' arrangement would last. I aim to fly the Lobster protein which has recently had wide media coverage.

Protein crystallisation in MicroG lost credibility in its early days due to over stating of its merits by some American Scientists. In recent years the experiments are being done more thoroughly and critically.  It is apparent that we are only now grasping how best to utilise the microgravity environment. Hence it would be a great shame if we would have to stop now when we have better understanding combined with possibilities of continuous access to the International Space station. Moreover for the British scientists, it would be a pity if others will reap the benefits of the effort that we have invested, while we will become bystanders.

Imperial Experiments in microgravity:

·        Crystallisation of Reverse transcriptase on the Russian Photon 7 ('Kashtan Mission')

·        Crystallisation of lysozyme on Spacehab 1

·        Crystallisation of crustacyanin on the IML-2 mission

·        Crystallisation of crustacyanin on the UMSL-2 mission

·        Crystallisation of crustacyanin on the LMS mission

PUBLICATIONS

·        Chayen, N.E., "Microgravity Protein Crystallisation Aboard the Photon Satellite" J. Cryst. Growth 153 (1995), 175-179.

·        Chayen, N.E., Gordon, E.J. and Zagalsky, P.F., "The Crystallisation of Apocrustacyanin C1 on the International Microgravity Laboratory (IML-2) Mission" Acta Cryst. D 52 (1996), 156-159.

·        Chayen, N.E., Snell, E.H., Helliwell, J.R. and Zagalsky, P.F., "CCD video Observation of Microgravity Crystallisation: Apocrustacyanin C1" J. Cryst.Growth 171 (1997), 219-225.

·        Snell, E.H., Cassetta, A., Helliwell, J.R., Boggon, T.J., Chayen, N.E., Weckert, E., Holzer, K., Schroer, K. Gordon, E.J. and Zagalsky, P.F., "Partial Improvement of Crystal Quality for Microgrvity Grown Apocrustacyanin C1" Acta Cryst. D  53 (1997), 231-239.

·        Ries Kautt, M., Broutin, I., Ducruix, A., Shepard, W., Kahn, R., Chayen, N., Blow, D., Paal, K., Littke, W., Lorber, B., Theobald-Dietrich, A. and Giege, R., "Crystallogenesis Studies in Microgravity with the Advanced Protein Crystallisation Facility on SpaceHab-01" J. Cryst. Growth 181 (1997), 79-96.

·        Boggon, T.J., Chayen, N.E., Snell, E.H., Dong J., Lautenschlager, P., Potthast, L., Siddons, P. Stojanoff, V., Gordon, E., Thompson, A., Zagalsky, P.F., Bi, R.C.and Helliwell, J.R., "Protein Crystal Movements and Fluid Flows During Growth" Phil. Trans. R. Soc. Lond. A. 356 (1998), 1045-1061.

·        Dong, J., Boggon, T.J., Chayen, N.E., Rafetry, J., Bi R-C and Helliwell, J.R., "Bound Solvent Structures for Microgravity, Ground Control, Gel and Microbatch Grown HEW Lysozyme Crystals at 1.8Å Resolution" Acta Cryst. D 55(1999) 745-752.

·        Snell, E.H., Chayen, N.E. and Helliwell, J.R., "Crystallisation of Biological Macromolecules in Microgravity" (1999). The Biochemist December issue 19-24.

·        Chayen, N.E. and Helliwell, J.R., "Space-grown Crystals May Prove their Worth"  Nature  398, (1999) 20.

·        Helliwell, J.R., Snell, E.H., Chayen, N.E., Judge, R.A., Boggon, T.J. and Pusey, M.L. "Fluid Physics and Macromolecular Crystal Growth in Microgravity" in "Physics of Fluids in Microgravity" Monti R. ed (2002)

·        Chayen, N.E. and Helliwell, J.R. (2002) "Protein Crystallization in Microgravity: Are We Reaping the Full Benefit of Outer Space?" New York Academy of Sciences in press.

What I have written above is a short summary of the situation. I can of course supply much more detail if necessary as well as references for all the statements made

Name

Prof. WT Coakley

Affiliation

Cardiff University

Address

School of Biosciences,

Cardiff University,

Main Building,

Cardiff CF10 3TL

Telephone

02920 874287

Fax