Cassandra Extavour may be the only professor in the Department of Molecular and Cellular Biology who is also a recorded musician. Her classically-trained soprano voice can be heard on the album Codex Huelgas: Misa Santa Maria La Real, recorded with the Spanish early music group Ensemble Huelgas. She has performed in operas, soloed in oratorios, and sung in choirs from Canada to Spain.
Artistic pursuits aside, fellow professor Andrew Murray describes her as an original thinker who is respected and admired by her students. In an interview she comes across as practical, honest, and straightforward, but with a ready, dry wit. In describing one performance as the witch for a production of Humperdinck’s opera Hansel and Gretel in the UK, she said of the role, “It suited me.”
Extavour was born in Toronto, Ontario. Both of her parents emigrated to Canada and met in Toronto – her mother from Switzerland, and her father from Trinidad. It was from her father, a percussionist, that Cassandra took her musical abilities. Although neither parent attended college, she and her siblings were encouraged to get as much education as they could.
“They didn’t pressure us to study anything specific,” she said. “Their goals for us were that we get at a minimum an undergraduate degree, that we become financially independent, that we fulfill any responsibilities that we chose to take on, and that we do something that we enjoy.”
Extavour began her undergraduate education at the University of Toronto with the intention of training to become a neurosurgeon.
“I had no interest in practicing medicine,” she said. “I had this idea that if I trained to be a neurosurgeon, maybe that would help me understand how the brain worked and how the brain directed human behavior. I thought that was interesting because I’d always thought that human behavior was terrible. And fascinating.”
It was not long before Extavour decided that the pre-med atmosphere was not for her. While she was motivated by curiosity and genuine interest in her courses, she perceived that many of her classmates were more interested in getting the best possible grades. She decided to switch to a molecular genetics major, but almost switched again when she became bored with her prerequisite biology classes and more interested in mathematics.
“In my third year of undergraduate work I took biochemistry as a requirement, and that was extremely interesting to me,” she said. “It was logical, and empirical, and quantitative, unlike most of the biology that I had been exposed to up until that point. So I decided to finish out the molecular genetics degree although I did get a second major in math because I just accumulated a bunch of math classes out of interest.”
From the vagaries of human behavior, Extavour’s interests had switched to genetics. She decided to continue with graduate work, but she admitted that she had very little idea of what a future in academic lab work would look like.
“I didn’t understand what being a graduate student meant,” she said. “I knew I needed to get lab experience, so I entered a lab as an undergraduate in the summer after my third year.”
This summer lab work, studying C. elegans, introduced Extavour to developmental biology. She found this new field very stimulating, but she did not want to plan her educational future around merely one new field of study.
“I knew that I wanted to leave the country and to be able to live in a different country and experience what it was like to live in a different language,” she said. “I knew a small amount of Spanish, partly from an introductory course I had taken out of interest, and partly from a lot of salsa dancing that I used to do at that time.”
Extavour knew she did not have the patience for plant or mouse genetics, and Spain did not have any C. elegans labs in 1995. Finally she discovered Antonio García-Bellido at the Autonomous University of Madrid, whose work she had already been exposed to in Toronto. He was working with Drosophila genetics, which Extavour knew would be at least as tractable a genetic system as C. elegans. More importantly, she had found a mentor who continued to develop her natural inclination for experimental rigor and creativity.
“It was an excellent experience,” she said. “He has been the single greatest scientific influence on me. I was very very lucky to become his student. He was a very strong and complex personality, and it was extremely challenging. It’s not a lab environment for everyone, but I learned a lot from him. Everything that I value about my scientific abilities, intellectually, I owe to him.”
While finishing her Ph.D in Spain, Extavour began to lose interest in studying single organisms, and hoped to expand her research into more generalizable theories in developmental biology. She wanted to find out if her observations on the genetic aspects of development would hold true across all kingdoms of life, and so she decided to pursue postdoctoral work in evolution and developmental biology at the Institute for Molecular Biology and Biotechnology in Greece and later at the University of Cambridge. However, even as she continued to discover new and exciting questions in science, she was still undecided about her future in research.
“When I was writing my thesis, I’d decided to leave science and pursue music full time,” she said. “That was my plan for about a year, as I was writing my thesis. Then kind of at the last minute, just after writing my thesis and defending it, I changed my mind and decided not to abandon science, at least not for the moment.”
For a few years her dual passions competed for supremacy. She won a research grant from the Biotechnology and Biological Sciences Research Council in the UK, and flew to Basel, Switzerland every few months to train with her voice teacher. In 2007 she wrote articles on the specification of germ cells and on gonadogenesis in Urbilateria, and also performed the demanding role of the Gingerbread Witch in Engelbert Humperdinck’s opera Hänsel und Gretel. In order to satisfy both interests, she eventually decided to focus on science full time and pursue music part time. Even after moving to Cambridge and establishing her lab at Harvard in 2007, she has managed to find time to sing with both the Handel and Haydn Society and Emmanuel Music, both professional ensembles in Boston.
In the meantime, her Harvard lab has produced promising research in embryonic development, germline specification, and the effect of insulin signalling on reproductive capacity in fruit flies.
“Fly ovaries, like all insect ovaries, are made of egg producing assembly lines called ovarioles,” she said. “The number of these ovarioles is highly variable. Some Drosophila species have single digit numbers of ovarioles, and some have over a hundred, so you can imagine the ones with lots of ovarioles lay lots of eggs.”
Extavour finds the study of fruit fly ovarioles especially interesting since the research can so easily intersect with larger issues in evolution, including the effect of environment on fecundity. This line of research has led to some field work in Hawaii, studying the vastly different ovariole numbers of closely related flies that live in different ecological niches.
“I prefer lab work because it is more controlled,” she said. “You have greater potential for true reproducibility in the lab as well. Having said that, I have very little field experience, and I am someone who enjoys new things. So who knows? Maybe the more I go into the field, the more I’ll like it.”
Probably the most well-known work to come from the lab has been on intercellular signalling during germ cell specification. Extavour herself had published a rather controversial paper in 2003, hypothesizing that inductive signalling was the ancestral mechanism for making germ cells in animals, rather than the more widely accepted theories that favored maternally inherited germ cell determinants over inductive signalling.
“When I started my lab, one of our major objectives was to see if I could find experimental evidence that more animals than just mice, which were considered the exception in using inductive signals to make germ cells, could and did use such signals to make their germ cells,” Extavour said. “That is why we have been working with so many different organisms. Before starting my lab I even worked on non-arthropods, such as sea urchins and sea anemones, to see if examining a wider range of animals than those traditionally used would reveal something about the ancestral nature of animal germ cell specification mechanisms.”
The lab’s work paid off last year in a piece for PNAS on bone morphogenetic protein (BMP) signalling in the cricket species Gryllus bimaculatus, and was further described in a piece published in the journal Development this year. The new paper continues to describe germ line segregation in crickets, focusing on the role of the transcription repressor gene Blimp-1. However, even before these publications, several developmental biology textbooks had already been updated to reflect the conclusions of Extavour’s 2003 paper.
Another promising research vein comes from the study of the insect gene oskar, first discovered in D. melanogaster about thirty years ago. oskar is a novel gene that seems to have evolved at least partially from noncoding DNA, so it represents an excellent case study for novel gene evolution. The gene first appeared before or around the same time as the evolutionary radiation of insects, approximately 600 million years ago, and does not seem to have a homolog in any other branch of animals. According to Extavour, oskar presents many opportunities for future research.
“Looking at oskar allows us to potentially study how new genes evolve from formerly noncoding regions and how new genes can contribute to the evolution of new developmental processes,” she said. “We also know that the same gene performs very different roles in different insects – in some insects it is required for making the germline, in other insects it is required for nervous system function.”
Extavour and her students have already published a handful of papers on oskar and its functions. For example, Extavour Lab alumna Abha Ahuja completed a molecular evolution analysis on oskar gene sequences from sixteen Drosophila species, hoping to shed light on the evolution of oskar’s role in germline specification. OEB student Ben Ewen-Campen, MCB student John Srouji, and postdoc Evelyn Schwager reported in Current Biology that oskar’s appearance predates the evolution of higher insects. The gene will no doubt continue to provide important avenues for student research under Extavour’s guidance, but she also hopes to broaden her lab’s research goals to include non-animal evolution.
“I started as an undergrad with C. elegans, but to be honest I’m finding working on animals to be limiting,” she said. “I’m looking for deeper, more general principles of gene function and evolution that are older than just animals. I don’t know exactly what the research program in my lab is going to look like in five years. I still think the biological question that is more interesting than any other is how two cells, with effectively identical genetic information, decide to do different things with that information. I still think that is the fundamental problem of developmental biology, and the most interesting problem to me.”
EVOLUTIONARY BIOLOGY PROFESSOR PURSUES SCIENCE AND SONG [CASSANDRA EXTAVOUR]
