SBNet

SBNet - Annual Report 1997

Summary.
The year 1997 was the first in which most of the Network was in, or came into, operation. At the end of the year, all (27) positions financed by the Network had been allocated. The last two rounds of student-position allocations (the "contingency fund" of the original proposal; four and three student positions, respectively) were made by the Board, based on peer-review of the proposals received from the PIs after open calls for applications. In June, the Network Coordinator was appointed, and in the same month the First Annual Conference of the Network was held in Tällberg, and turned out a tremendous success. The mentor system was also set up, and the first student-mentor meetings took place during the Conference.

Board.
Early in 1997, Prof. Uli Hacksell (Astra Draco, Göteborg) announced that his increased workload made it impossible for him to stay on as a member of the SBNet Board. In his place, Dr. Jan Hoflack (Astra SCL, Mölndal) was co-opted. The other Board members stayed on: Dr. Björn O. Nilsson (Pharmacia & Upjohn; Chair), Prof. Guy G. Dodson, F.R.S. (University of York), and Prof. Iain D. Campbell, F.R.S. (University of Oxford). The Programme Director, Prof. T. Alwyn Jones, F.R.S. (Uppsala University), continued to function as a non-voting qualitate quo member of the Board. The main responsibilities of the Board involve: strategic directions, finances, and peer-review. The Board met twice during 1997 (In February in Windsor, and in December in London); in the future, it will continue to meet twice a year, once during the Annual Conference (in Sweden), and once in the Winter (in the U.K. if possible). Important matters that arise in between meetings are dealt with by means of electronic mail or telephone conversations. Matters involving the day-to-day running of the Network are handled by the Chair, Director, and Coordinator.

Allocations.
During 1997, the Board allocated the remaining seven student positions (these constituted the "contingency fund" of the original proposal). This process took place in two rounds ("tranches"), for both of which open calls for applications were issued. For Tranche 3 (four positions), the Board decided that preference would be given to proposals that were based on a multidisciplinary approach and/or involved a collaboration with industrial or other laboratories. In addition, the Board decided to set priorities in four strategic research areas, namely integral membrane and receptor proteins, drug design, structures of high medical relevance, and methods development (in any of the areas of structural biology). Twenty proposals were received and reviewed by the Board (excluding the Director). After this process, the following four proposals were selected for funding:

For Tranche 4 (three positions), the quality of the applications, as determined by the score in the peer-review process, was the most important overall criterion. In case of equal scores, PIs that were not already funded by the Network were to be prioritised. Proposals that involved collaboration with another network or programme funded by the Foundation for Strategic Research were viewed upon favourably. A total of 25, often excellent, applications was received, many more than there were positions available. After a difficult review process, the Board decided to award the student positions to:
In retrospect, essentially all seven "contingency fund" positions have been awarded to young and talented people who were not operating independently (in Sweden) at the time of writing of the original proposal. It can therefore be concluded that the idea of having a contingency fund was an excellent one, and that it worked extremely well in practice to foster new efforts by young and promising scientists.

Positions funded.
SBNet presently funds the position of 27 structural biologists in Sweden, which constitutes a fair share of the community (estimate: ~15%). Appendix I contains a list of all positions and the PIs to whom they have been allocated. Seven positions have not been filled yet. Of the remaining 20 positions, 9 are taken up by females (45%). Twenty positions are student positions (74%), and four are researcher positions (15%). Two of the remaining three positions have been allocated to the Uppsala expression laboratory, and the final position is that of the Network Coordinator.
In terms of disciplines, 15 positions are related to X-ray crystallography, 7 to NMR, 2 to electron microscopy, one to modelling, and two to the expression laboratory. In terms of geographical spread, LU and SLU have each been awarded 3 student and 2 researcher positions, KI and UU both have 5 student positions, KTH has 2 student positions, and SU and UmU each have one student position. In addition, the Network Coordinator and the expression laboratory personnel all resort administratively under Uppsala University. Since all students have been working one and a half years or less, no Ph.D.s have been awarded to any of them yet. The first Ph.D. to be "produced" by the Network is Tomas Hansson (UU, PI Åqvist) in May, 1998.
The position of Network Coordinator was advertised in the Spring of 1997 (until that time, Dr. Gerard J. Kleywegt, UU, acted as ad interim Coordinator). Three applications for this position were received. They were reviewed by the Chair, and he recommended that Dr. Gerard J. Kleywegt be appointed. Unfortunately, Uppsala University has been unwilling to promise to take over this position after SSF funding ceases. Hence, the position is one as "forskare" rather than "lektor", despite the fact that the Coordinator possesses both "lektorskompetens" and "professorskompetens".

Graduate training.
Due to the fact that the Network Coordinator was not appointed until June, 1997, no SBNet-specific graduate courses have been organised yet. Nevertheless, there have been several developments in this area involving the Network in 1997:

Mentor system.
For the students who are funded through the first two allocation rounds, a mentor system was set up in 1997. The idea of the mentor system is to assign two mentors to each student funded through the Network. Student and mentors meet at least once a year, at the Annual Conference of the Network, to discuss the student's progress, problems, new ideas, etc. In order to obtain a large enough pool of mentors, all PIs who have been allocated one or more positions are required to act as mentors. In addition, many other PIs, both from industry and academia, have volunteered as mentors, which is a very encouraging development, in line with the increased spirit of cooperation and collaboration that the Network seems to have engendered! The pool of mentors is now indeed sufficiently large to also provide two mentors for each of the students funded through the last two rounds of allocations. In order to target the mentor system more precisely (a wish expressed by the PIs at the First Annual Conference), the Board is currently reviewing both the initial experiences and the expectations of the students who have had their first student-mentor meetings.

First Annual Conference.
For many Swedish structural biologists, the First Annual Conference (held from 6 to 9 June, 1997, in Tällberg) has been the first tangible spin-off of the Network. Although organised by volunteers and under great time pressure (the Network Coordinator position had not been filled yet), the Conference proceeded not only without a flaw, it was also an enormous success, judging from all the positive feedback received from both speakers and participants during and after the meeting. The format of the Conference was similar to that employed during Gordon Research Conferences, with morning and evening lecture sessions. Each session included one or two renowned foreign speakers and further talks by Swedish students and post-docs. A summary of the programme is given in Appendix II.
The meeting was attended by 120 people (the maximum number that could be accommodated), both PIs and students, from all disciplines of structural biology, from academia and industry, and from all over the country. The atmosphere was extremely friendly, enthusiastic, and one of community, and many new contacts have been made across the borders of disciplines and institutes. Students and post-docs had been offered a very attractive conference fee provided they presented a poster. This resulted in a high-quality session in which over 70 posters were presented. The Pharmacia & Upjohn Poster Award for the best poster went to Mathias Eriksson, SLU ("Ribonucleotide reductase"). Also the lectures (both by the invited speakers and by the young persons) were generally of high quality. The Astra Structural Chemistry Laboratory Award for the best presentation by a young person went to Helena Berglund, KTH ("Structural studies of the ribosomal protein S15").

Internal and external communication.
For the intra-Network communication, two major instruments are used. The first is the SBNet mailing list (sbnet@xray.bmc.uu.se), through which the Swedish structural biology community is regularly informed about Network matters (e.g., calls for proposals by related SSF-funded networks, Network Conference), scientific matters (e.g., upcoming conferences, new software), educational matters (e.g., upcoming courses), and more. The current mailing list contains addresses of around 150 Swedish structural biologists (PIs, researchers, post-docs, students).
The second instrument, which is also the Network's "face" to the outside world, is the SBNet site on the World-Wide Web (URL: http://xray.bmc.uu.se/sbnet/). This site is updated continuously (typically, two or three times a week) and contains a large amount of information about and related to the Network. The site has been "advertised" by contacts with related networks and organisations, by submitting it to some of the major web-based search engines, and through a short article in the newsletter of the Protein Data Bank.
The mailing list and the web-site, together with the First Annual Conference, have made that SBNet is now generally considered to be "the hub" of Swedish structural biology.

Travel grants.
In order to foster inter-laboratory collaboration, the Network operates a scheme under which students and post-docs can apply for funding for laboratory-rotation visits (e.g., if a student from Lund wishes to visit the NMR group in Umeå).
Starting in 1998, the Board has also allocated funds for foreign travel awards. These awards are intended to fund travel and subsistence for a trip (1-4 weeks) to a foreign centre-of-excellence in any of the areas of (or related to) structural biology. The purpose of the trip must be to acquire expertise or know-how that is not readily available within Sweden itself. Candidates who receive an award should write a short report of their trip (this report will be published on the SBNet web-site), and be prepared to travel to other interested laboratories in Sweden to give a presentation about the results of their trip.

Collaborations with industry.
The structural biologists from the industrial laboratories at Pharmacia & Upjohn and Astra are active and valued participants in the Network (e.g., annual conference, mailing list, mentor system). Some of the student positions sponsored by SBNet also involve close collaboration between industry and academia. During 1997, several students and post-docs from Swedish structural biology laboratories have found employment in industrial laboratories. In the future, the Network also intends to involve the industrial participants more closely in its educational activities (e.g., through a workshop on drug design co-organised by industrial scientists). Such initiatives are beneficial to both students (who get to know leading scientists in Swedish industry) and the industrial scientists (who get to know students interested in their line of research). The Network will also attempt to attract industrial scientists from companies that are not (yet) actively involved in structural biology research (e.g., the wood and cellulose industry) to its second annual conference.

International collaborations.
Essentially all groups that participate in the Network have national and international collaborations, and many participate in one or more EU-funded programmes. Since these collaborations usually arise from personal networking, merits, and research interests, the Network does not play a significant role in this process. However, through the SBNet WWW site, occasionally a request comes in from foreign scientists interested in collaborations with Swedish structural biologists. Such requests are brought to the attention of the participants by posting them on the SBNet WWW site.

Scientific reporting.
The students and scientists supported through SBNet have written a report of their research activities during 1997. These reports were bundled with the mid-term evaluation report that has been submitted to SSF. In addition, the reports will be made available through the SBNet WWW site.

Abbreviations.
KI, Karolinska Institute
KTH, Royal Institute of Technology
KVA, Royal Academy of Sciences
LU, Lund University
SBNet, Structural Biology Network
SLU, Swedish University of Agricultural Sciences
SSF, Swedish Foundation for Strategic Research
SU, Stockholm University
UmU, Umeå University
UU, Uppsala University

Appendix I.

The following persons/positions are funded through SBNet:

(1) Network Coordinator

Name: Gerard Kleywegt
Position:
Network Coordinator/Researcher
Projects:
Structural Neurobiology / Protein Crystallography / Structural Bioinformatics
Gender:
M
Actual starting date:
1 June, 1997
Administrative starting date:
1 June, 1997

(2) Expression Laboratory Uppsala

Name: Eva Davey
Position:
Laboratory Assistant
Gender:
F
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

Name: Petra Franzén
Position:
Laboratory Engineer
Gender:
F
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

(3) Researchers ("Forskare")

Name: Bryan Finn
PI:
Forsén (LU)
Project:
Protein structure and dynamics
Gender:
M
Actual starting date:
1 January, 1997
Administrative starting date:
1 July, 1996

Name: Stefan Knight
PI:
Eklund (SLU)
Project:
Structure/function studies of virulence associated adhesion organelles from pathogenic Gram negative bacteria
Gender:
M
Actual starting date:
1 January, 1997
Administrative starting date:
1 January, 1997

Name: Jan Saras
PI:
Mowbray/Jones (SLU/UU)
Project:
Structural studies on membrane protein receptors
Gender:
M
Actual starting date:
1 August, 1997
Administrative starting date:
1 July, 1997

Name: (being appointed)
PI:
A. Liljas (LU)
Project:
Crystallography at MAX II

(4) Ph.D. students

Name: Patrik Andersson
PI:
Otting (KI)
Project:
NMR spectroscopy of large proteins
Gender:
M
Mentors:
Härd, Finn
Actual starting date:
15 April, 1996
Administrative starting date:
1 July, 1996

Name: (being appointed)
PI:
Jones/Mowbray (UU/SLU)
Project:
Structural studies of the platelet-derived growth-factor receptors
Mentors:
Lindqvist, Hebert

Name: Stefan Bäckström
PI:
Schneider (KI)
Project:
Structural studies of vesicle-transport proteins
Gender:
M
Mentors:
Mowbray, Andersson
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

Name: Tomas Hansson
PI:
Åqvist (UU)
Project:
Computational approaches to ligand design and enzyme catalysis
Gender:
M
Mentors:
L. Nilsson, Schneider
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

Name: Andreas Muranyi
PI:
Forsén (LU)
Project:
Solution structures of blood coagulation protein domains
Gender:
M
Mentors:
Otting, Härd
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

Name: Maria Selmer
PI:
A. Liljas (LU)
Project:
Structural studies on ribosomal proteins and RNA and their complexes
Gender:
F
Mentors:
Nordlund, Unge
Actual starting date:
1 July, 1996
Administrative starting date:
1 July, 1996

Name: Louise Kraft
PI:
Lindqvist (KI)
Project:
Structural studies of vesicle-transport proteins
Gender:
F
Mentors:
L. Liljas, Åqvist
Actual starting date:
1 October, 1996
Administrative starting date:
1 July, 1996

Name: Henrik Hansson
PI:
Härd (KTH)
Project:
Protein-protein interactions
Gender:
M
Mentors:
Wijmenga, Hård
Actual starting date:
1 December, 1996
Administrative starting date:
1 January, 1997

Name: Magnus Wolf-Watz
PI:
Härd (KTH)
Project:
Structure and dynamics of proteins in solution
Gender:
M
Mentors:
Forsén, Kördel
Actual starting date:
1 February, 1997
Administrative starting date:
1 January, 1997

Name: Agnes Rinaldo-Matthis
PI:
Nordlund (SU)
Project:
Structural studies on protein phosphatases
Gender:
F
Mentors:
A. Liljas, Ladenstein
Actual starting date:
1 February, 1997
Administrative starting date:
1 January, 1997

Name: Charlotte Axblom
PI:
L. Liljas (UU)
Project:
Structure of viruses and viral components
Gender:
F
Mentors:
Schneider, Hebert
Actual starting date:
1 March, 1997
Administrative starting date:
1 January, 1997

Name: Devapriya Choudhury
PI:
Eklund (SLU)
Project:
Ribonucleotide reductase holoenzyme complexes
Gender:
M
Mentors:
A. Liljas, Lundqvist
Actual starting date:
1 March, 1997
Administrative starting date:
1 January, 1997

Name: (being appointed)
PI:
Hebert (KI)
Project:
Electron crystallography of microsomal glutathione transferase
Mentors:
Jones, Eklund

Name: (being appointed)
PI:
Cheng (KI)
Project:
Structural studies on virus-host interactions

Name: Susanna Törnroth
PI:
Iwata (UU)
Project:
Structural studies of human multidrug resistance protein (MDR)
and multidrug resistance-associated protein (MRP)
Gender:
F
Actual starting date:
1 September, 1997
Administrative starting date:
1 July, 1997

Name: (being appointed)
PI:
Kleywegt (UU)
Project:
Crystallographic studies of monoamine oxidase, a drug target in the treatment of clinical depression and Parkinson's disease

Name: Jenny Cromsigt
PI:
Wijmenga (UmU)
Project:
Development of methods for improved structure determination of larger systems by means of NMR
Gender:
F
Actual starting date:
1 July, 1997
Administrative starting date:
1 July, 1997

Name: Ines Munoz
PI:
Ståhlberg (SLU)
Project:
Structural studies of cellulases and other enzymes with potential for use in the cellulose industry and bio-organic synthesis
Gender:
F
Actual starting date:
1 October, 1997
Administrative starting date:
1 January, 1998

Name: (being appointed)
PI:
Akke (LU)
Project:
Protein structural dynamics, interactions and drug design

Name: (being appointed)
PI:
Knight (SLU)
Project:
Structure/function studies of virulence associated adhesion organelles from pathogenic Gram negative bacteria

Appendix II.

The programme of the First Annual Conference of the Network was as follows:

Friday, June 6
20:00-20:30piano recital by Tom Taylor (if you're a Bartok-fan)
20:30-??mixer (if you're a bar-tokfan)

Saturday, June 7
09:00-09:10opening of the Conference (Björn Nilsson, Chairman SBNet Board)

09:10-12:30Session A: X-ray Techniques & Applications
Organiser: Gerard Kleywegt (Uppsala Univ.)
09:10-10:10Randy Read (Univ. of Alberta)
"Getting better structures faster with maximum likelihood"
10:10-10:30Ramaswamy Subramanian (Swedish Univ. of Agricultural Sciences)
"Elucidation of stereoselective binding in liver ADH - an application of
maximum likelihood refinement"
11:00-11:20Thomas Ursby (Lund Univ.)
"Improved estimation of structure factor difference amplitudes from
poorly accurate data"
11:20-11:40Tom Taylor (Uppsala Univ.)
"Validation"
11:40-12:00Helena Käck (KI)
"Time-resolved studies of an ATP dependent carboxylase: dethiobiotin
synthetase"
12:00-12:30Uwe Sauer (Swedish Univ. of Agricultural Sciences)
"Phenylalanine hydroxylase - a MAD story"

14:00-16:00Network meeting (PIs)
17:00-18:00football match
19:30-21:30Session B: Challenges for Structural Biology
Organiser: Björn Nilsson (Pharmacia & Upjohn)
19:30-20:20Jan Hoflack (Astra)
"Structural investigations on myo-inositol monophosphatase"
20:20-20:30Leg-stretching break (not leg-breaking stretch !)
20:30-20:50Tomas Hansson (Uppsala Univ.)
"Receptor-ligand binding affinities from dynamic simulations"
20:50-21:10Hans Andersson (Uppsala Univ.)
"Expression, purification, characterisation and inhibition studies of the
simian immunodeficiency virus reverse transcriptase (RT)"
21:10-21:30Michael Sundström (Pharmacia & Upjohn)
"Structural basis for growth hormone receptor activation"

Sunday, June 8
10:00-15:00put up posters

09:00-12:20Session C: Membrane Proteins
Organiser: So Iwata (Uppsala Univ.)
09:00-09:50Werner Kühlbrandt (EMBL Heidelberg)
"Structure determination of membrane proteins by electron
cryo-microscopy"
09:50-10:10Ken Xian (KI)
"Three-dimensional reconstruction of membrane bound porcine
H,K-ATPase from negatively stained 2D crystals"
10:10-10:30Arne Elofsson (Stockholm Univ.)
"Architecture of helix bundle membrane proteins. An analysis of
cytochrome c oxidase from bovine mitochondria"
11:00-11:50Christian Ostermeier (Yale Univ.)
"Antibody fragment mediated crystallization and structure of the
bacterial cytochrome c oxidase"
11:50-12:20So Iwata (Uppsala Univ.)
"New approaches in crystallization and crystallography of membrane
proteins"14:00-14:30student-mentor meetings (1)
14:30-15:00student-mentor meetings (2)
15:00-17:30poster session

19:30-21:40Session D: Hot Structures
Organiser: Alwyn Jones (Uppsala Univ.)
19:30-20:20Tim Richmond (ETH Zürich)
"The structure of the nucleosome core particle at 2.8 Å resolution"
20:20-20:40Jill Sigrell (Uppsala Univ.)
"E. coli ribokinase - A new fold gives new ideas about kinase function"
20:40-21:00Björn Kauppi (Swedish Univ. of Agricultural Sciences)
"Naphthalene 1,2-dioxygenase crystal structure at 2.5 Å resolution"
21:00-21:20Peter Agback (KTH)
"NMR structure of a SSO7d-DNA complex"
21:20-21:40Cristofer Enroth (KI)
"The X-ray structure of phenol hydroxylase from Trichosporon
cutaneum
"
21:40"SBNet Pharmacia & Upjohn Best Poster Award" (Johan Kördel,
Pharmacia & Upjohn)

Monday, June 9

09:00-12:30Session E: NMR Techniques & Applications
Organiser: Johan Kördel (Pharmacia & Upjohn)
09:00-09:50Jim Omichinski (IBI-2 Forschungszentrum Jülich)
"Labelling, purification and DNA complex formation of transcription
factors for NMR studies as applied to the zinc finger proteins GATA-1
and GAGA"
09:50-10:10Patrik Andersson (KI)
"Isolation and NMR analysis of a deuterated, 15N-labelled 45 kDa
gyrase B fragment"
10:10-10:30Magnus Wolf-Watz (KTH)
"Initial biophysical studies of PEBP2aB"11:00-11:50Nico Tjandra (NIH)
"Taking advantage of asymmetry in protein structure determination
by NMR"
11:50-12:10Helena Berglund (KTH)
"Structural studies of the ribosomal protein S15"
12:10-12:30Göran Larsson (Umeå Univ.)
"Structural basis for the calmodulin interaction with transcription factor
SEF2-1"

12:30-12:50* meeting summary (Carl-Ivar Brändén)
* "Astra Structural Chemistry Laboratory Award" for the best oral
presentation by a young person (Bob Carter, Astra Hässle)

Appendix III.

The financial report for 1997 is appended as a one-page spreadsheet as designed by the Foundation. Since our Network is subject to mid-term evaluation this year, we have not included estimates of "actual cost" (including commitments in kind, etc.), as per the instructions received from the Foundation.
Compared to the budget for 1997, the expenses have been quite a bit lower than projected. This is due to a number of factors:

However, all expenses not incurred yet during 1997 are locked as future commitments.
Some other minor comments on the budget:


SBNet Latest update at 31 March, 1998.