E.N. Baker (New Zealand, president of the IUCr)

"A small country can have a succesful protein crystallography group too"

Protein crystallography in 

- future directions

- specific ways of cooperation, sharing of programmes, specific workshops, visits to specific labs, access to particular resources...?

- regional cooperation?

- what are the technical means and is there access to synchrotrons?

- is there an interested community supporting you, in molecular biology, biotechnology, pharmacology, industry?

- teaching of protein crystallography at graduate or post-graduate level

Ted set up macro-molecular crystallography in New Zealand in the 1970s, with very small resources. His outline of essentials:

Most important: Desire to do it; a belief in the role of Structural Biology..

Requirements:

1) A supportive biological community.

This support often needs to be "earned". You need to demonstrate both that YOU can solve structures, and to educate the community into recognising the insights that structure can give. The recognition is easier now, the need to show tha t you are competent remains. (The other problem is that it is hard work over expressing and purifying protein, and whilst collaborators are often willing perhaps to advise you, you may have to do the hard slog.)

2) Facilities for data collection/calculations

a) there needs to some way to characterise crystals. This may be done with any available generator and camera set up

b) you need to be able to freeze crystals ready for transfer to a synchroton.

(There was a long discussion on synchroton availabilty; Zbyszek Dauter said that Brookhaven is thinking of setting up "FEDEX" data collection facilities; you send your crystal and the data set is returned to you. Daresbury has already s et up a trial scheme for this and others will probably follow. But this will require resources for staff at the synchrotons, and it is not clear how Eastern European labs were to apply. Most synchrotons take applications from anywhere, but only pay travel costs for those with affiliation. East European participation has to be discussed!)

c) Computing resources, both hardware and software.

Most people felt their resources were workable; much software is free; hardware is fairly cheap. Access to the internet is a bit variable.

3) Overcoming the psychological barrier.

When you hear of big American labs doing things faster and bigger it is easy to lose heart. It is important to remember that there are many areas where structural biology is valuable, and as someone said " just because it isn't signal t ransduction that doesn't mean it isn't interesting".

Ted's suggestions with some commentary:

1)Start with an accessible problem. Success helps a great deal with collaborators/politicians/funding agencies/potential students.

2) Good students are the best resource. Helpful, innovative, enthusiastic..

3) Priorities for in-house equipment : X-ray generator, crystal freezing, computing.

4) Important to maintain outside collaborations. Will need travel money.

Center for Biocrystallographic Research established in Poznan, including both the Academy of Sciences and the University.

The Center, housed in new Academy buildings, was funded by the Foundation for Polish Science in 1994. This is a non-government body which funds one new research initiative each year.

The Centre obtained ~ 400,000 dollars.

Crystallography group already in existence.

The laboratory is "open" - in addition to carrying its own research it also serves as a centre of integration and promotion for biostructural sciences in Poland. It welcomes visitors from within and outside Poland to come to learn biocr ystallographic techniques or to collaborate on biostructural projects of mutual interest.

Facilities:

Protein purification

Crystallisation room

300mm Mar Image plate

Work stations

RNA/DNA chemical synthesis

Poznan has a super-computing centre

Synchroton resources available at Hamburg, Lund, USA, Lure - local contact helps. Gets time but no travel money

People: 3 staff, 1 Post-doc, 3 PhD students, 3 students, 2 tech. support

Salaries paid by University/Academy are very low; they are supplemented by grants.

All encouraged to travel.

Projects:

Hard at first to get local biochemists interested, but now more projects than they can handle:

• L-asparaginases (bacterial, yeast, plant)
• thiol proteases/inhibitors
• retroviral protease
• SAH hydrolase
• myoglobin mutants
• pathogenesis-related proteins
• RNA-dependent RNA polymerase
• nucleic acids constituents and fragments

Research funds:

Local: salaries ( low)

Institutional research funds - low. Two policies, either all members of staff get the same, or (better he feels!) it is related to scientific output.

Govt expenditure 0.47% of GNP for science in Poland (and falling!)

Industry : local = 0.0

overseas companies: not interested..

Best funds from overseas bodies; Howard Hughes.

They must teach:

Use Internet courses from Birkbeck (some support from Brirish Council, Soros)

Not bad relationship between Academy and University.

Quite optimistic.

Slovak Academy of Sciences: no internal funds apart from salary.

Almost accidental interest in crystallisation, starting from a biochemical product.

Projects: Rnase Sa, Glu. Amylase, Rnase Sa / Barstar.

All crystallography done abroad till recently (York, Hamburg)

Environment - not much interest, but the EC-Copernicus initiative has helped a lot.

( Should say; very agreeable meeting at Smolenice in April with lots of biochemists..)

People at University now interested; small molecule resouce exists.

Problem is personnel; without travel money such as Copernicus provided, it will be harder to maintain interest.

Funding: Political climate not interested in science.

$2000 per person per annum; not enough for basic chemicals.

Computing OK, data collection in-house impossible.

His funds at present: Howard Hughes, but this finishes next year.

No access to EU yet for Slovakia.

Biggest problem: salaries - very low; people leave to get a living wage. Average age in Academy has gone from 27 years to 48 years; younger people have to be very dedicated or have rich spouses to continue.

Did PhD in Munich, finished 1993, and still has useful links and collaborations. In the past, many students sent abroad to learn about structure but he is the only one to come back!

Obtained a grant of $500 000 in 1996 sufficient to buy all necessary equipment.

Important things for raising a grant:

Biological connections (his father heads a group in Slovenia!)

To make a successful grant application though needed a crystallographer too.

A lot of politics associated with getting grants. Favoured sons in the god-father sense.

Lucky in position within Europe, 4 hours only to drive to Munich

Problems about returning to Slovenia: Everything takes longer; hard to keep scientific career alive. Inflation whittles away actual funds steadily.

Academy hostile to Universities.

Also:

Heirachy of science set up 20 or more years ago, when structural biology scarcely existed. Needs to be restructured, but a very hard thing to do.

Hard to get post-docs to come to Slovenia, rather than Western Europe.

Depends on (good) PhD students, but their education eats into Dusan's time. (Later he said he was particularly interested in intensive training courses for students..)

Future?

The society has little interest or respect for science.

There is some industrial money though..

Very interested in raising grants from abroad.

Same problem as others for funding.

Competition between the Academy and Universities. Not much interest in sharing resources.

There are 2 funding agencies: No useful communication between them and distribution of funds chaotic. Bohdan is depressed by this, and does not have any idea how the situation could be changed.

The whole scientific effort is short of funds: the whole academy gets ~ 500, 000 dollars to divide between all workers.). Very minimal investment from industrial concerns. Most Czech pharmeceutical companies bought up by Western compani es and research budgets cut or abandoned. This means salaries are low, and it is hard to attract or keep good students. Also a problem of convincing the biochemists that structure can give insights.

On the positive side:

Several labs. have interesting projects requiring structural biology.

Usual path is that proteins and other material sent abroad, where collaborators may or may not treat it with care. Not really a satisfactory way to work.

A grant of some 400 000 dollars has been obtained by Juraj Sedlacek to buy a generator and an Image plate. These will be installed in the near future.

Solutions?

1) To go abroad yourself.

2) There are local resources sufficient to characterise crystals. Synchroton time available.

Boris says situation should make him pessimistic, but he thinks things will get better. War disastrous for all science / priorities change! Some young researchers were sent abroad, (but will they come back?)

Money short, salaries low, grants low.

Politicians in small countries fell science is unimportant - but encouraged by the NZ outlook! International pressure can help

Tradition of small molecule crystallography. Macromolecular group set up in 1994 with 2 (young) staff members, 4 PhD students. No prospect of more staff positions, and they have to do a lot of teaching.

Facilities:

Raxis

Old cryro system about to be replaced.

OK for access to synchrotons

Projects:

Xylose isomerase

Trypsin/ chymotrypsin mutants

Calmodulin/drug complexes

Oligonucleotides

Oxford (wilmos Fulop ) collaboration on protease II

Colaborations

Oxford/ Portugal

Some industrial money.

Funds for Collaborations?

Some infrastructure up and running seems to need ~ 500,000 dollars

Not enough funds available in local economies; have to wait for these to recover.

Low salaries mean brain drain inevitable.

Marius Jaskolski (and others) subsidises local salaries from overseas grants.

He started with very limited funds; things still worked, but more slowly. Important not to be too worried by this.

All funds for travel money and for workshops. People felt this had been useful.

Other contribution had been to educate biologists in the value of structure.

(Interesting: Slovaks and Russians had not come to Prague - no money!

We must apply pressure to ECM to reduce registration fees and grant travel funds to those whom the organising cttee know need it.. eg: Lunin )

Some funds for travel, organisation of workshops, fellowships and joint doctorates.

EU - Framework 5.

Doesn't look very good for Eastern Europe but Royal Society believes there is every opportunity to influence the ministers and to establish the principle of financial support for scientific communities outside the EU.

Associate members can join in with networks; but nothing specifically for interchange. Anita points out that associate members are not eligible anyway any more for special funds.

Guy Dodson is now on an Eastern European cttee (don’t have exact title)

He urged people to establish their own networks and approach Royal Soc. with proposals to help these function. Mariusz J. will establish links.

NATO, Soros Foundation, Howard Hughes ...

The ESF and FEBS can help with workshops. EMBO offers fellowships. Could the EMBL be persuaded to provide travel funds for access to synchrotrons?

Anita - will ask for guidance from EU

Guy - more details on Royal Soc things

Mariusz - network