Schistosome Genome Initiative

Dave Johnston daj at nhm.ac.uk
Wed May 8 06:23:00 EST 1996


Dear Schistosome Researcher,

Some 2 years ago, WHO assembled a group of Schistosome researchers to plan the first 
stages of a WHO Schistosome Genome Project. Initial priorities were identified as the 
support of "Preliminary work on sequencing of the schistosome genome....... with the 
longer term aim of concentrating efforts on characterization of target areas of the 
genome". Since then, a variety of gene discovery and physical mapping approaches have 
been initiated for both S. mansoni and S. japonicum.

WHO have asked Network members to meet together again, this summer, to review 
progress and to plan for the future. The meeting's aims include (1) to review 
specific progress and future plans within each of the existing WHO-funded projects 
(2) to examine problems that have been encountered and explore ways to overcome them 
(3) to foster existing collaborations and communication (4) to encourage other 
members of the Schistosome Research Community to join the Network, to participate in 
its research activities and to exploit existing results and resources (5) to discuss 
the future development of the Network and the future direction(s) of the Genome 
Project (6) to determine data management priorities (within WHO's existing 
framework). The meeting is being organised by Mette Strand (Network Chair), David 
Johnston (Network Secretary) and Jucara Parra (Local Organiser, Centro de Pesquisas 
Rene Rachou, Av. Augusto de Lima, Belo Horizonte, Minas Gerais, Brasil, email 
jparra at cenargen.embrapa.br, fax 55-31-295-3115). We  initially scheduled the meeting 
to be held in Ouro Preto, Brasil from 31st July  to 2nd August (delegates arriving 
30th July, departing 3rd August), planning to include the proceedings of the meeting 
in a report to be submitted to WHO by 25th August. However, due to the deadline for 
submission of NEW applications (23rd July), we are investigating whether it will be 
possible to bring the meeting forward by approximately one month (we apologise that, 
if the meeting is rescheduled for the end of June, it will be such short notice). 
Further details, a definite date and location and a specific agenda will be posted in 
the next few days

 WHO's workplan for the Schistosoma Genome Initiative is reproduced below (for the 
full text, see 
gopher://gopher.who.ch:70/00/.anonymousftp/programme/tdr/docbase/workplan/par_geno.tx
t (or access via http://www.who.org/programmes/WHOProgrammes.html under TDR gopher 
information)).

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
WHO WORKPLAN START

RATIONALE
The Parasite Genome Committee was created for coordination of research on the 
analysis and mapping of genomes of the TDR target parasites.  The sequenced genome 
map of the parasite will provide a powerful tool for identification and cloning of 
target genes for vaccines, diagnostics and drug development.  Understanding the 
mechanisms of drug resistance and various functions of the parasite is enormously 
facilitated with known genome sequence.  Development of physical maps is the first 
step and a one-time investment to serve the scientific community.  It is understood, 
that TDR can provide only a fraction of the funds required for such high technology 
research, therefore, a close collaboration with other institutions would be 
necessary.

OBJECTIVES
The activities of the Parasite Genome Committee are carried out by five networks 
corresponding to the target parasites: Filaria, Leishmania, Trypanosoma brucei, T. 
cruzi and Schistosoma. Malaria and leprosy are not included because there are 
independent networks for the Plasmodium and M. leprae genomes which are being 
supported outside TDR.    Each network has a workplan that has been agreed upon by 
the Committee.  In all the networks, much emphasis will be put on the development of 
a common database system, and on the training and participation of Disease Endemic 
Country (DEC) scientists, to produce low resolution maps of the genome of the five 
parasites and promote gene manipulation techniques.
 
PROGRESS AND EXPECTED OUTCOMES
During the first year of Parasite Genome activity, five networks have been set up and 
consolidated.  Planning meetings have been held to select parasite strains for 
research and to draw up guidelines towards attaining the Programme's objectives.  All 
networks successfully fulfilled an important task to construct parasite stage 
specific cDNA and large fragment genome libraries (YAC, BAC, Cosmids).  Thousands of 
EST and chromosome markers have been obtained and the process of chromosome mapping 
was initiated. Significant expansion of these activities is expected during the next 
biennium, in the hope that with the introduction of high precision robotics the 
genomes of the representative parasites will be sequenced within the next 5 years.
         
POSSIBILITIES FOR COLLABORATION IN WORKPLAN OBJECTIVES
Research proposals with budgets up to US$50 000 addressing one of the 
objectives mentioned above are invited.  Projects are funded for three years after 
which investigators should reapply, either for a continuation or for a new line of 
research.  At this point, competitive proposals are encouraged to assure continuation 
of particularly interesting research leads but the Committee will not fund parallel 
work at different institutions.  Interested investigators should consult with the 
Committee manager before applying.

HOW TO APPLY
Researchers interested in collaborating  in the above mentioned activities should 
request application forms from the Communications department of 
TDR. [Email: TDRNEWS at WHO.CH]

Next proposal deadline: 23 July 1996

All specific correspondence related to research covered by the Parasite Genome 
Committee should be sent to:

Dr B. Dobrokhotov
Manager of the Parasite Genome Committee UNDP/World Bank/WHO Special Programme for 
Research and Training in Tropical Diseases (TDR),
World Health Organization,
20 Avenue Appia,
CH-1211 Geneva 27, Switzerland
Tel: (41.22) 791.3816/3724
Fax: (41.22) 791.4854
Internet: Dobrokhotovb at WHO.CH

THE SCHISTOSOME GENOME PROJECT WORKPLAN FOR 1996-1997
Coordinator: Dr Mette Strand (mette_strand at qmail.bs.jhu.edu)
 
The Schistosoma genome network has selected S. mansoni and S. japonicum.  Priority 
has been given to four objectives towards mapping of the schistosome genome: 1) 
Resource development; stage-specific cDNA libraries are available, however, 
development of large fragment genomic libraries is needed; 2) Gene discovery, 
including identification of stage-specific genes; 3) low resolution physical mapping; 
and 4) development of genome databank. 

OBJECTIVES, PLANNED ACTIVITIES AND STATUS

1. Resource Development
a)Development of stage-specific cDNA libraries
1. Cercariae
2. Schistosomula
3. Juvenile worms
4. Female adult worms
5. Male adult worms
6. Egg
Stage-specific libraries are available, however only libraries #2, 4 and 6 are in 
phagemids. Criteria for new libraries: Directional library in phagemids; cDNA inserts 
>500bp average cDNA inserts>1000bp, 1000000 or greater recombinants 95% of 
recombinants should contain  specific insert <1% of recombinants should contain 
insert of host origin, RDNA or mitochondia transcripts. The majority of sequencing 
has been carried with adult worm libraries

b) Development of large fragment genomic libraries
1) YACs---Available
2) Cosmids ---To be initiated

2. Gene Discovery
a) Expressed sequence tags (ESTs)
-Identify genes from different developmental stages by use of Subtractive libraries 
and Differential Display techniques---1400 EST sequenced, 640 new genes identified
-Identification of rare mRNAs---To be initiated
     
3. Chromosome Mapping
Generate low resolution physical map---To be initiated
a) YAC hybridization
-Map cosmids and individual genes----Preliminary stage, screening
b) Cosmid hybridization
-Map genes to cosmids, Generate linkage maps- ---To be initiated in 1996
c) Molecular characterization of chromosome structure
-Map YACs to chromosomes to develop contigs for each chromosome (FISH, CISS, PRINS)

4. Development of Genome Databank
-Standardize information and create genomic database available via Internet---To be 
created in 1996

WHO WORKPLAN END
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

WHO are very keen to encourage growth of the Network, and to receive applications for 
new projects/new collaborations for the third year of the Initiative (January 1997 
onwards). If your group is interested in joining the Network, submitting an 
application, contacting potential collaborators, or attending the meeting, please 
will you write, fax or eMail David Johnston (Dept. of Zoology, The Natural History 
Museum, Cromwell Road, London SW7 5BD, UK, tel 44 171 9389297, fax 44 171 938 8754, 
eMail daj at nhm.ac.uk) AS SOON AS POSSIBLE to register your interest. Jucara Parra will 
be in London from 7/5/96 to 20/5/95 and we hope to be able to formalise most of the 
plans for the meeting during her visit. Further details, a definite date and location 
and a specific agenda will be circulated in the next few days. Financial arrangements 
are still to be finalised, however, WHO have set aside a sum of money to help cover 
meeting costs and FIOCRUZ have generously offered to help sponsor accommodation and 
food. It is therefore hoped that we will be able to partially assist new groups to 
attend the meeting, join the Network and participate in new collaborative grant 
applications.

We look forward to hearing from you,

J Parra
D Johnston
M Strand

DAJ
David A Johnston
Secretary to the SCHISTOSOME Genome Network,
Biomedical Parasitology Division, Dept. of Zoology,
The Natural History Museum, Cromwell Road, London SW7 5BD.

tel: 0171 9389297 (from outside UK: 44 171 9389297)
fax: 0171 9388754 (from outside UK: 44 171 9388754)
eMail daj at nhm.ac.uk






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