The Worm

Sydney Brenner

"Most people viewed C. elegans almost as a joke organism

and, adding insult to insult, often confused it with the flatworm"

In 1974, Sydney Brenner, the "father of the worm" published a historical manuscript in which he introduced a new model organism, the nematode C. elegans, to geneticists. For "their discoveries concerning genetic regulation of organ development and programmed cell death" using C. elegans, Brenner, together with C. elegans scientists H. Robert Horvitz and John Sulston, was awarded the 2002 Nobel prize in Physiology or Medicine, justifying the use of C. elegans in biomedical research.

I first met the worm, at an EMBO course on model organisms where it directly caught my attention. It was the first time I saw this tiny creature moving elegantly and glowing green due to its transparent body and the green fluorescent protein (GFP) it was expressing.

Soon I realized that the simplicity of its nervous system (it only has 302* neurons and 959 somatic cells) and short generation time (only 3 days) were a great match for my impatience. Also, the interest I had in genetics and the fact that the "connectome" of the worm neuronal system was already mapped (see also WormWiring) made C. elegans an ideal system to study questions related to neuronal development and function.

"The worm won't take you high on the scientific ladder", colleagues told me before I decided to join Marty Chalfie's lab at Columbia University. I was advised to go to a mouse lab and do more hardcore science. Somewhat insecure in my decision, I followed my intuition.

I have spent the last 15 years of my life happily probing these little creatures and being part of the most friendly scientific community I could have dreamt off. In 2008 Marty was awarded the Nobel prize in Chemistry for his introduction of GFP as a biological marker, which ironically was one of the first things that had caught my attention.

The worms received a third Nobel Prize, the Nobel Prize in Physiology or Medicine 2006 which was awarded to C. elegans scientists Craig C. Mello and Andrew Z. Fire "for their discovery of RNA interference - gene silencing by double-stranded RNA."

You can learn more about the worm at Wormbook and Wormbase.

* newer reports present evidence suggesting that the 2 CAN cells are not neurons

My contribution

My scientific journey using C. elegans as a model system has been fascinating and gratifying. Some of the findings include:

Ectopic expression of SID-1 in neurons enhances neuronal RNAi (equal contribution with Andrea Calixto & Dattananda Chelur). Nature Methods

Neuronal cell fate can be challenged by inappropriate expression of effector genes in different cell types expressing common selector genes. PNAS

The transcription factor (TF) Aristaless/ALR-1 possesses a new TF activity that restricts variable gene expression and ensures proper differentiation. PNAS

The alpha-tubulin acetyltransferase MEC-17 regulates microtubule organization and neuronal structure (equal contribution with Charles Keller and Nereo Kalebic). Current Biology

A newly identified protein (EIPR-1) is part of the endosome-associated recycling protein (EARP) complex and EARP and EIPR-1 are involved in dense core vesicle maturation. PLOS GEN

The NALCN/Nca (NCA-1 and NCA-2) ion channel functions downstream of Gq and Rho to regulate locomotion. Genetics

The GPCR kinase GRK-2 negatively regulates the D2-type dopamine receptor, DOP-3, and this activity positively modulates the function of the NALCN/Nca ion channel. PLOS GEN