My broad research interest is the evolution of conserved developmental genes and their paradoxical contribution to the diverse morphology, developmental trajectories and life history traits in the animal kingdom. I believe that there is still a lot to be learned about the basis of developmental mechanisms by detailed study of organisms other than the established models.
My previous work related to the evo/devo field has focused on the evolution of Hox genes in the Nematoda. More recently this has extended to other protostome taxa including a species of tardigrade (water bear) that I and Mark Blaxter (Edinburgh) and his coworkers have begun to develop as a developmental model.Currently I am focussing on the evolution of PAR gene function.
Two major questions in developmental biology are: i) How are the earliest aymmeteries in development leading to the differential morphology observed along the body axis established? ii) How do highly conserved genes evolve to contribute to diversity? By looking at the conserved set of par (partitioning defective) genes and their associates (pkc-3, atypical protein kinase 3 and cdc42, a Rho-like GTPase) in two non-model organsisms we hope to contribute to answering both these questions.
First encountered in Caenorhabditis elegans the par genes (and subsequently pkc-3 and cdc42) and their homologs in other species have been implicated in establishing cell asymmetries in a number of contexts. It appears that together they represent a universal mechanism for establishing asymmetry in animal cells. Perhaps most surprisingly these genes are clearly involved in the establishment of early developmental polarity (i.e before the first mitotioc division) in both major invertebrate model organisms, Caenorhabditis elegans and Drosophila melanogaster. This raises the intriguing and exciting possibility that two animals, with very different approaches to development (the deterministic worm vs the regulative fly) share a conserved ancestral mechanism for the very earliest steps in axial patterning.
We propose to exploit this possibility by looking at the role of par genes and their associates in a crustacean (Paryhale hawaiensis) and a tardigrade (Hypsibius dujardini). If as we suspect the role of par genes is conserved in early polarity they represent a set of conserved genes that can be used to gain an insight into the evolution of the earliest molecular events in development.
The conserved nature of these genes means they can be identified using standard techniques for cloning developmental genes. Both P. hawaiensis and H. dujardini (like the fly and worm) are members of the major protostome clade the Ecdysozoa and would therefore be expected to use par genes for setting up early polarity if this is a conserved ancestral mechanism. They have been chosen as their phylogenetic positions are informative and because they are both potentially fruitful models for studies of the evolution of development. I have already cloned homologs of 3 par genes from the tardigrade H. dujardini, the most distant of our two chosen species from the models to prove this approach is feasible. We will conduct a sereies of experiments using gene expression analyses, cell-fate mapping and RNA interference to assay function to investigate the role of the par genes in these two species. The results of these experiments will tell us whether (as we suspect) the role of par genes in early polarity is conserved and result in a detailed description of early asymmetry (and related embryology) for previously understudied taxa (tardigrades and crustaceans).
In addition to these conclusions we hope to be able to build testable hypotheses as to how a conserved core of genes (involved in orchestrating the cytoskeleton and positioning early posterior and anterior determinants to polasrise the one cell stage) has evolved to maintain this role across a diverse array of organisms. Implicit in this is a need to explain the molecular evolutionary processes that have occurred to allow this conserved set of genes to interact with taxa specific downstream determinants, such as Drosphila oskar.
Publications:
Learning impairments induced by glutamate blockade using dizocilpine (MK-801) in monkeys.
Harder JA, Aboobaker AA, Hodgetts TC, Ridley RM. Br J Pharmacol 1998 Nov;125(5):1013-8
Medical significance of Caenorhabditis elegans.
Aboobaker AA, Blaxter ML. Ann Med 2000 Feb; 32(1):23-30
Hybridization to high-density filter arrays of a Brugia malayi BAC library with biotinylated oligonucleotides and PCR products. Foster JM, Kamal IH, Daub J, Swan MC, Ingram JR, Ganatra M, Ware J, Guiliano D, Aboobaker AA, Moran L, Blaxter M, Slatko BE. Biotechniques 2001 Jun;30(6):1216-28
Hox gene loss during dynamic evolution of the nematode cluster. Aboobaker AA, Blaxter ML, Current Biology 2003 Jan, 13, 37-40.
Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Aboobaker AA, Blaxter ML, Molecular and Biochmeical Parasitology 129, (2003) 41-51.
Hox gene evolution in nematodes: novelty conserved. Aboobaker AA, Blaxter ML,
Curr Opin Genet Dev. (2003); 13(6): 593-8.
Functional Genomics for parasitic helminths and nematodes. Aboobaker AA, Blaxter ML, Trends in Parasitology. (2004) (4): 178-184.
Presentations:
• World Health Organisation, Switzerland, working group meeting for Tropical Disease Research, Oct 2003. “Prospects for RNAi as a direct method for drug target validation in filarial nematodes”
• College of Veterinary Medicine, Cornell University, host Professor Judith Appleton, Aug 2003. “Time for functional genomics in helminth parasites
• Natural History Museum, Copenghagen, host Professor Reinhardt Kristiansen, 2002, “Early work in establishing tardigrades as a possible model system: Hox genes like those of arthropods”
• Cold Spring Harbor, Evolution of Development and Diversity, 2002, “Nematode Hox genes”
• University of Reading, hosts Prof Peter Holland/ Dr David Ferrier, 2002, “Nematode, Nematomorph and Tardigrade Hox genes”
• World Health Organisation Filarial Parasite Summit Meetimg, Bernard Nocht Institute, Hamburg, 2001. “ The utility of RNAi and other functional genomics approaches in helminth parasites”
• Helminth Parasite Keystone meeting, Taos, New Mexico 2000, “Hox genes from the filarial parasite Brugia malayi.
Education and Research experience:
University of California Berkeley, USA (Oct 2003-Sept. 2005)
Wellcome Trust International Research Fellow, “How do the molecular processes establishing the earliest asymmetries in development evolve? Investigating the conserved roles of PAR genes in a crustacean and a tardigrade.”
HHMI Postdoctoral Fellow (Oct 2003-Dec 2003)
New England Biolabs, USA (May 2003- Sept. 2003)
Visiting Research Scholar, “Functional genomics in the human filarial parasite Brugia malayi and its’ Wolbachia endosymbiont”
Department of Genetics, University of Barcelona, Spain (March 2003- May 2003)
Visiting Researcher (Host Prof. Emili Salo), “Planarian Flatworm Regeneration”
Institute for Cell Animal and Poulation Biology, University of Edinburgh, UK (Oct 1997- March 2003)
Wellcome Trust Prize Fellowship .
“Towards the development of the tardigrade Isohypsibius Ed (Hypsibius dujardini) as a new model in the Ecdysozoa”
(Oct 2001- March 2003)
Wellcome Trust 4 year Prize PhD studentship.
“The Cellular and Molecular basis for Human Disease Processes”
(Oct 1997- Oct 2001)
Ph.D, thesis: “Hox genes from nematodes and RNAi in Brugia malayi”
Supervisor: Dr Mark Blaxter, Nematode Genomics Lab, ICAPB, University of Edinburgh.
(Oct 1998- Oct 2001) Ph.D viva examination passed in February 2002.
Girton College, University of Cambridge,
BA, honours in Natural Sciences, honours year in Genetics,
University of Cambridge.
1994-1997
Wellcome trust Vacation Scholarship "The effect of glutamate blockade using dizocilpine (MK-801) on motor activity and accuracy in monkeys."
1996
