Abu Dhabi NYU provost using worm to unlock genetic secrets

A tiny, see-through worm may not seem the most promising place to look for clues about how a single cell turns into a whole organism. But that is the hope of Dr Fabio Piano, the provost at New York University Abu Dhabi and founding director of NYU's Centre for Genomics and Systems Biology in New York. He, and dozens of other scientists, now have in their possession the world's first genetic "blueprint" of the Caenorhabditis elegans nematode roundworm. And they believe they are close to uncovering a simple key behind the worm's development: a hidden network of protein "foremen" that move around the worm as it grows, telling its genes when they are needed. C. elegans has long been a favourite of geneticists, representing, in Prof Piano's words, the "ideal model organism". Its skin is transparent, making it easy to see and photograph. As the worms ovulate, as their eggs are fertilised, as the cells divide; everything is visible right down to the level of individual cells and their nuclei. The worms breed and grow quickly. An egg takes just three days to develop into a mature adult - so tests that require many generations of observations can be easily conducted within a practical time-frame. Mutate a gene, and within a week you can see what has changed. Add to that a more unusual feature of the worm's biology: unlike most animals, C. elegans has an almost entirely consistent cell fate map. During its development, scientists know exactly which cells will divide to form which other cells. The pattern is the same in every individual, resulting in the same 959 cells, in exactly the same places. When you look at a cell, it is easy to know which one you are looking at, and where it came from. That is the result of a precisely choreographed development sequence. As the worm grows, each cell must divide at the right time, in the right direction, in the right manner. And that requires precise instructions about how and when to start and stop dividing. Prof Piano's team studied that division using RNA interference (RNAi) - a technique that can be used to block a single gene, to see what happens (or what does not). The basic genetics of C. elegans have long been known - its genome was fully sequenced as far back as 1998. More elusive, though, was what all 20,000 of its genes actually did. Which proteins did they code for, and what functions did they carry out in the worms' cells? In the normal functioning of a cell, each DNA (deoxyribonucleic acid) gene is transcribed into a unique RNA (ribonucleic acid) molecule, each of which then produces a specific protein. It is this second stage - the production of protein by RNA - which is blocked by RNAi. With the basic genome already described, Prof Piano and his collaborators set about the painstaking task of using RNAi to knock out each of the 20,000 genes in turn. "We depleted the function of every single gene, one by one, to see what would happen and then wrote a dictionary explaining each function, kind of like parts of a car." They found that of the 20,000 genes, just half were being expressed in the early developing embryo, while the other half are likely expressed later in development and in the worm's adult life. They also studied the interactions between the various proteins, and between the genes and proteins. Putting this together allowed them to draw up a "network" map - essentially a flowchart of each gene, the RNA transcribed from it, the protein produced by that, and the function of each protein. Some proteins act as structural elements; others as signalling enzymes that cause or allow other processes to happen.