All tags Epigenetics Scientist of the month: Victor Ambros

Scientist of the month: Victor Ambros

Victor Ambros tells us about his lab's discovery of the first miRNA in 1993, and also talks about some of his more recent research.

Brief biography

Victor Ambros, PhD

Victor Ambros grew up in Vermont, and graduated from MIT in 1975 with a degree in Biology. He did his PhD research (1975–1979) with David Baltimore, studying polio virus genome structure and replication.

Victor began to study genetic pathways controlling developmental timing in the nematode Caenorhabditis elegans (C. elegans) while he was a postdoc in Bob Horvitz's lab (1979–1984), and he continued studies of C. elegans development while on the faculty of Harvard (1984–1992) and Dartmouth (1992–present).

In 1993, Victor and coworkers Rosalind Lee and Rhonda Feinbaum described the first miRNA, the product of the lin-4 gene of C. elegans. Since then, the role of miRNAs in animal development has been a major focus of Victor's research.

What sparked your passion for science?

I grew up in Vermont under dark skies, and as a kid I dreamed of being an astronomer. I also collected rocks and minerals, and for a while I thought I might explore the moon someday. But, in college I fell in love with molecular biology and developmental biology, and never looked back.

The first miRNA was identified in 1993 in your lab. Can you tell us about how that discovery came about?

We were not looking for miRNAs, but rather we were only trying to understand how the lin-4 gene works. lin-4 mutant worms have very interesting developmental timing defects, suggesting that the lin-4 gene product might be part of a biological timing mechanism.

So, we wanted to identify and characterize the lin-4 gene product — which we fully expected would be a protein. But when we cloned the lin-4 locus, were were surprised to find out that lin-4 did not encode a protein, but rather produced a little 22 nucleotide lin-4 RNA.

After we stumbled upon the lin-4 miRNA, we became obsessed by this little RNA, and by trying to understand how it works. Since then, most of the lab's research has had something to do with miRNAs and their roles in animal development.

What progress has been made in microRNA expression profiling since then?

Wow! Huge changes. When we started studying miRNAs, the only ways to assay them were RNAse protection or northern blots. These were semi-quantitative methods at best, and you needed 10 micrograms of total RNA er sample, and you could only assay one miRNA at a time.

With current technology, such as Firefly, one can assay hundreds of miRNAs at once, using orders of magnitude less RNA per sample, and get fantastically accurate quantitative data.

What exciting research projects are currently occurring in your lab?

We are very excited about using C. elegans to explore how miRNAs are integrated into gene regulatory networks such that they confer biological robustness against everyday stresses such as temperature change, dietary stress or bacterial infection.

Where do you see things going in the next 5–10 years?

Impossible to imagine! I am terrible at forecasting the future, but can say for sure that living things will continue to astonish us with their elegance and complexity for a very long time.

One thing you could not live without (inside or outside the lab)?

Rosalind Lee! She is indispensable both inside and outside the lab. Rosalind is my wife (since 1976), lab manager and collaborator (first author on the 1993 lin-4 paper).


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