Research Interests:

For the past few years we have been studying the evolution of body size in nematodes. We aim to understand both evolutionary and developmental mechanisms; to do this we use a range of tools from gene knockouts to mathematical models. Most of our work is on the nematode Caenorhabditis elegans, but we also use a whole zoo of relatives (at least 50 spp.) all of which are small (0.5 - 3.0mm long) and easy to grow in the lab. Below, is a brief summary of some of our projects.

Figure 1: Caenorhabditis elegans

Why nematodes moult
Mavji Patel, Ricardo Azevedo, Henrik Jensen

More than 1000 scientists work on C. elegans, and the sequencing of the entire genome was completed in December '98. Yet until we did it, no-one had ever measured the growth of the worm -- at least not carefully. When we did so, we en passant solved one of the Great Mysteries of Wormology namely, why nematodes moult. Henrik Jensen, a statistical physicist, is helping us model the biomechanics of worm growth.

Many Cells, Big Cells, No Cells
Chris Knight, Anthony Flemming, Ana Cunha

To understand the genetic control of growth in C. elegans (or its evolution in the nematodes) we have break down the rather complex phenotype of "body size" into its cellular components. C.elegans is ideal for this. We can count cells and trace lineages. We can watch cells go through their cell cycles in the living worm, and measure them while they do it. We can look at how some nuclei undergo endoreduplication (somatic polyploidization) -- and we can do all these things not only in C. elegans, but also in a host of other species in order to find out precisely why some worms (be they mutants or evolved species) differ from others in body size.

Long, thin, worms
Zai-Zhong Shen, Mavji Patel

Nearly all C. elegans developmental genetics has been concerned with pattern formation. But we're interested in growth. A few body size and shape genes have already been identified (in the TGF-beta pathway), and we've done a 50,000 genome EMS mutagenesis screen for more. We found 18 new mutants in 4 new genes that give a long, thin, worm: lon-4, lon-5, lon-6, lon-7. We're mapping them and cloning them and making doubles to see how they interact with other dwarfism and gigantism genes. We think that they will prove to be key players in the feedback loop that must, somehow, control worm growth. We are cloning these genes in collaboration with Simon Tuck at Umea, Sweden.


Decline and Fall of the Platonic Worm
Ana Cunha, Ricardo Azevedo, Rodney Coleman

Everyone knows that nematodes have invariant cell lineages; that's why they're so loved by developmental biologists. But do they? We actually examined this by counting lots of cells in lots of worms (12 species) and found that some nematodes have hugely variable epidermal cell numbers -- implying variable lineages. To understand this better we built some computer models and are working with a mathematician, Rodney Coleman, to get some formal theory on how branching processes generate variance.


Pygmy worms
Ricardo Azevedo, Chris Knight

The canonical wildtype C. elegans (N2) is 1200µm long. But another wild strain, RW7000, is 800µm long. To identify the genetic basis of this difference -- and learn something about the genetics of natural populations -- we did a QTL mapping study and have identified a single body size QTL on LGIV; we're now mapping this further to clone it. We're also surveying other wild strains for more pygmy genes. One day, we hope to study human pygmies as well.

 


Mutants!
Ricardo Azevedo, Camilla Lauren-Määttä

Furthering the theme of population genetics of body size, we want to know something about the distribution of mutations that affect body size as well as the way in which such mutants affect fitness. To do this we are using a set of Mutation Accumulation lines kindly given to us by Peter Keightley (Edinburgh) and Larissa Vassileva + Michael Lynch (Oregon) as well as lines that Ricardo selected up and down for 50 generations. It seems that most mutants decrease body size. We plan to do mutation accumulation experiments in other nematode species as well, to see how general our results are.


Who We Are:

Selected Publications:

Braun, V., R.B.R. Azevedo, M. Gumbel, P-M. Agapow, A.M. Leroi, H.P.Meinzer. 2002.
ALES: a cell lineage analysis and mapping of developmental events.
Bioinformatics 1: 1-8

Azevedo RB, Keightley PD, Lauren-Maatta C, Vassilieva LL, Lynch M, Leroi AM. 2002.
Spontaneous mutational variation for body size in Caenorhabditis elegans.
Genetics 162:755-65.

Morita K, Flemming AJ, Sugihara Y, Mochii M, Suzuki Y, Yoshida S, Wood WB, Kohara Y, Leroi AM, Ueno N. 2002.
A Caenorhabditis elegans TGF-beta, DBL-1, controls the expression of LON-1, a PR-related protein, that regulates polyploidization and body length.
Embo J. 21:1063-73.

Nystrom J, Shen ZZ, Aili M, Flemming AJ, Leroi A.M., Tuck S. 2002.
Increased or decreased levels of Caenorhabditis elegans lon-3, a gene encoding a collagen, cause reciprocal changes in body length.
Genetics.161: 83-97.

Knight, C.. G., M. N. Patel, R. B. R. Azevedo, and A. M. Leroi. 2002.
A novel mode of ecdysozoan growth in Caenorhabditis elegans
Evolution and Development 4: 16-27

Patel, M., C.G. Knight, C. Karageorghi, A.M. Leroi. 2002.
Evolution of germline signals that control growth and ageing in nematodes
Proceedings of the National Academy of Sciences, USA 99: 769-774

Knight, C.G., R.B.R Azevedo, A.M. Leroi. 2001.
Testing life-history pleiotropy in Caenorhabditis elegans.
Evolution 55: 1795-1804

Azevedo, R. B. R. & A. M. Leroi. 2001.
A power law for cells
Proceedings of the National Academy of Sciences, USA 98: 5699-5704

Flemming, AJ, Shen, ZZ, Cunha, A, Emmons, SW, Leroi, A.M. 2000.
Somatic polyploidization and cellular proliferation drive body size evolution in nematodes.
Proceedings of the National Academy of Sciences, USA. 97: 5285-5290

Cunha, A, Azevedo, RBR, Emmons, SW, Leroi, A.M. 1999.
Variable cell number in nematodes.
Nature 402: 253-253 (Brief Communication)

Leroi, A.M., A. F. Bennett, and R. E. Lenski. 1994.
Heat acclimation increases high temperature survival in Escherichia coli.
Proceedings of the National Academy of Sciences, USA 91: 1917 - 1921

Leroi, A.M., M. R. Rose, and G. V. Lauder. 1994.
Can the comparative method reveal adaptation?
American Naturalist 143: 381 - 402.

Media:
The London Times (Higher Education Supplement) Feb 7, 1997

Other Activities:
Editorial Board of Evolution and Development
Occasional journalism for The London Review of Books and The Times Literary Supplement

Worm Links:
C. elegans at S.W.Texas
C. elegans at Sanger Centre
C. elegans chip at Stanford
Wildworms at NYU
Wildworms at Gent

Contact Details:
Dr AM Leroi
Department of Biological Sciences
Imperial College at Silwood Park
Ascot
Berks SL5 7PY
UK

Tel:
(020) 7594 2396 (office)
(020) 7594 2335 (lab)

Fax:
(020) 7594 2339

e-mail: a.leroi@ic.ac.uk