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Naming & shaming & sequencing the ‘Apicomplexans’

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Presentation on theme: "Naming & shaming & sequencing the ‘Apicomplexans’"— Presentation transcript:

1 Naming & shaming & sequencing the ‘Apicomplexans’

2 Outline of the presentation
Eukaryotic pathogen sequencing in Sanger ‘Apicomplexans’ – ‘the culprits’! Sequencing Plasmodium in Sanger Plasmodium biology: what makes P. falciparum unique Comparitive genomics Insights from other Apicomplexan genomes (theileria)

3 Eukaryotic Pathogen Sequencing in PSU

4 Why ‘Apicomplexans’?

5 The Apical Complex

6 The Apicoplast Eukaryote cell cyanobacterium Ancient algae chloroplast
Modern plasmodium Apicoplast DNA from apicoplast migrates to nucleus Algae forms symbiotic relationship with host

7

8 Naming & shaming the ‘Apicomplexans’

9 The World of Apicomplexans!
Intestinal disease in mammals Parasitise brain/ kidney of rodent Malaria Tropical theileriosis Babesiosis Periph. eosinophilia (30%) Brain infection (Chinchila) Parasitises heart muscle/brain Toxoplasmosis parasitic disease of falcolns bowel diease in human Coccidiosis Insect gut parasites Cryptosporidiosis Dog parasites Oyster parasite

10 Euk. pathogen sequencing projects in PSU
Apicomplexan sequencing projects in PSU X 3

11 The Plasmodia X 3 P. falciparum (Gardner et al 2002)
P. reichenowi (3x shotgun in progress) P. vivax (full sequencing in progress) P. cynomolgi P. knowlesi (8x shotgun, complete) P. gallinaceum (3x shotgun in progress) P. berghei (Complete sequencing in progress) P. yoelii (5.6x, Carlton et al 2002) P. chabaudi (8x shotgun, in progress) X 3

12 One child die of P. falciparum malaria in sub-Saharan Africa every 30 seconds

13 Comparitive genomics: P. falciparum & rodent malarias
(Neil Hall)

14 The Chromosomes of P. falciparum
telomere Subtelomeric repeats VAR genes RIFIN / STEVOR genes Other gene families Rep20 TARE2-5 antigenic variation House-keeping antigenic variation VAR genes Rifin

15 P. falciparum & P. vivax: sub-telomeric species-specific gene families

16 Erythrocytic forms of P. falciparum
Rings Mature Trophs

17 Adhesive domains of pfEMP-1 (var gene)
Extracellular TM Intracellular DBL-1 DBL-2 DBL-3 DBL-4 ATS a b d e g DBL-5 Blood Group A antigen CR1 GAG’s CD36 IgM ICAM-1 CD31 CSA CIDR C2 TM pfEMP-1 ( kDa) var (8-15 kb) Exon II Exon I

18 Whole genome domain organisation of pfEMP1 proteins
59 var genes in total. Expressed on red cell surface and involved in sequestration 3 types of domain. DBL- duffy binding like CIDR- cystine rich interdomain region C2 - constant2

19 Telomeric var gene organisation
Telomeric var genes tend to be type 1 All internal var clusters tend to be type 1 Three upstream conserved sequences present UPSa – 11 members- Inverted vars UPSb -35 members - telomeric vars UPSc 13 members - Internal vars

20 Internal var clusters Five chromosomes have internal var genes
All internal var clusters tend to be type 1 GC-rich elements (202 bp) associated with all internal var gene clusters (42 % G+C) No GC-rich element in telomeric var genes Form secondary structure? Function?

21 Comparitive genomics: synteny breaks
EBL-1 (erythrocyte invasion) P. falciparum P. knowlesi P. yoelii P. falciparum P. knowlesi P. yoelii ACT-comparison of orthologous chromosomes between P. falciparum (human), P. knowlesi (monkey) and P. yoelii (mouse).

22 Subtelomeric gene families in malaria
falciparum reichenowi gallinaceum chabaudi berghei yoelii yir/cir/bir 138 180 838 pyst-a 1 - 108 45 168 pyst-b 10 34 57 pyst-c 5 4 21 pyst-d 17 pcst-f 2 pcst-g 75 11 7 pcst-h 6 Var 59 >100* Rifin/stevor 177 >100

23 Summary

24 Sequencing Project Management Administration Analysis & Databases
Carol Churcher Becky Atkin Karen Brooks Inna Cherevach Tracey Chillingworth Paul Davis Nancy Hamlin Kay Jagels Sharon Moule Brian White Sally Whitehead Karen Mungall Ian Goodhead Zahra Hance Heidi Hauser Mandy Sanders Mark Simmonds Danielle Walker Project Management Bart Barrell Julian Parkhill Neil Hall Stephen Bentley Matthew Berriman Al Ivens Marie-Adèle Rajandream Nick Thomson Administration Yvonne Shaw Sarah L.ocke Analysis & Databases Martin Aslett Andrew Berry Ulrike Böhme Ana Cerdeño Lisa Crossman Christiane Fowler Matthew Holden Arnab Pain Chris Peacock Hubert Renauld Mohammed Sebaihia Valerie Wood Barbara Harris Andrew Barron Louise Clark Craig Corton Jonathan Doggett Nicola Lennard Alexandra Line Doug Ormond Microarrays Celine Carret Theresa Feltwell Maria Fookes Nefeli Nikolaidou- Katsaridou Matloob Qureshi Jason Skelton Programming David Harper Rob Davies Arnaud Kerhornou Paul Mooney Kim Rutherford Ellen Scofield Adrian Tivey Ed Zuiderwijk David Harris Nigel Fosker Arlette Goble Lee Murphy Susan O’Neil Simon Rutter David Saunders Kathy Seeger Robert Squares Comparative Genomics Alison Dennis Emily Kay Helena Seth-Smith Subcloning Mike Quail  Angela Lord Halina Norbertczak Claire Price Ester Rabbinowitsch John Woodward

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