Dr. Carmen Coelho

Qualifications

PhD, Tata Institute of Fundamental Research, Mumbai

Research Area

Organ and Body Size
Growth and Development
Cell Competition

Research

The laboratory investigates the determinants of organ and body size in invertebrates and vertebrates, using the fruit fly Drosophila melanogaster as a model system.

Much of the work focuses on the growth of the wing imaginal discs, epithelial sac-like structures that grow and become patterned during larval development before differentiating to form the wings during pupation.

Recent work has shown that growth curves of the wing discs vary during normal development, with considerable variation in disc size during early larval life. This variation is compensated for during development and decreases towards the end of larval life.

These findings suggest that growth rates at a given stage may depend on the developmental history or growth path of an organ rather than simply on its size at that particular time.

Organ Growth & Size Regulation

Growth-Rate-Dependent Regulation

Mathematical models have been fitted to experimental data to investigate how variation in disc size during development may be reduced through growth-rate-dependent synthesis of hypothetical inhibitors.

Simulations indicate that appropriate final size may be achieved without continuously sensing organ size throughout development.

Early Growth and Final Size

Current work is examining assumptions concerning very early growth, including the period immediately following larval hatching.

One prediction being tested is that if size is altered at the very beginning of development, before growth begins, the alteration may not be compensated for and could result in an abnormal final size.

This also suggests that egg size could influence final disc size. The laboratory is therefore examining egg size under different culture conditions.

Cell Competition

A parallel line of research investigates the mechanisms underlying cell competition, a phenomenon first described in fly imaginal discs and subsequently demonstrated across species, including in early mouse embryos.

Cell competition is a process in which faster-growing cells eliminate their slower-growing neighbours. The phenomenon has also been implicated in cancer progression.

Genetic screens in the fly system have identified genes that are upregulated in slower-growing cells, or "losers", during cell competition.

It has been proposed that faster-growing cells, or "winners", secrete factors that signal to and eliminate the neighbouring "loser" cells. The identity of these factors remains an important area of investigation.

Identifying the Signals Behind Cell Competition

The laboratory is undertaking a genetic screen designed to provide an alternative approach to previously performed screens and potentially identify the factors involved in communication between competing cell populations.

Relevance to Human Health

These studies provide a platform for investigating biological processes relevant to human health and nutrition.

Catch-up growth is an established phenomenon in mammals, including humans and laboratory rodents. Variations in early growth caused by clinical or environmental factors do not always result in significant changes in final body or organ size.

Since growth is a fundamental process likely to be governed by conserved mechanisms, studies in the fruit fly may help guide investigations of growth regulation in humans.

Research on cell competition may also contribute to understanding overgrowth disorders associated with somatic mutations that result in mosaicism. The laboratory is beginning to mimic such mutations in flies to examine their growth properties in a simple and tractable system.

Selected Publications

Growth and cell survival are unevenly impaired in pixie mutant wing discs. Coelho CMA, Kolevski B, Bunn C, Walker C, Dahanukar A, Leevers SJ.
Development, 132: 5411–5424, 2005.
Do growth and cell division rates determine cell size in multicellular organisms? Coelho CM, Leevers SJ.
Journal of Cell Science, 113: 2927–2934, 2000.