Research

The lab’s research program focuses on understanding the dazzling diversity in the living world. We look at closely related species and try to determine how changes in developmental programs, gene expression levels and DNA sequences have led to phenotypic variation.

Gene regulatory evolution during the maternal-zygotic transition

One of the first gifts we receive from our mothers is our maternal RNA, which we use as embryos before we’re capable of making our own RNA. However, we soon stake out our independence, and not only begin transcribing RNA but also selectively destroy mom’s hand-me-downs through RNA degradation. This period in embryogenesis is referred to as the maternal-zygotic transition (MZT).

These processes – maternal RNA deposition and degradation, and zygotic genome activation – occur across the animal kingdom, but the details differ. While a postdoctoral researcher in the Lott lab, I analyzed the evolution of the MZT across the Drosophila genus, using transcriptomic analytical techniques that I had previously learnt in the study of Hymenoptera in the Johnson lab. We are continuing to look at related questions in my new lab. We are particularly interested in is how the MZT is regulated, how this regulatory information in encoded in the genome, and how evolutionary changes in the MZT can result from changes in genomic sequence.

Transposable elements in development, evolution and disease

So-called “jumping genes” were first discovered by Barbara McClintock in the middle of the last century. These rambunctious nucleotide sequences can make multiple copies of themselves within a genome and can spread through a population with surprising rapidity. Recent research has shown that transposition in the germline has played a role in a number of key evolutionary changes on the tree of life. Transposition in somatic cells, on the other hand, can lead to diseases ranging from schizophrenia to cancer.

The effect of transposition, in both the soma and the germline, has not been adequately modeled. We will be considering the extent to which transposable elements have shaped regulatory changes involved in zygotic genome activation. On a more general level, we will develop algorithms for simulating how the invasion of a transposable element can shape the genome and reconfigure gene regulatory networks.

Egg-laying with an edge

Sometime around 2008, an insidious pest invaded North America and quickly caught the attention of farmers throughout the western states and provinces. At first glance, there is little to distinguish the invader, Drosophila suzukii, from a myriad of other fly species, but a closer look reveals that a key innovation – the serrated ovipositor – sets it apart. D. suzukii’s ovipositor (see the images below) is elongated and endowed with sharp bristles, enabling it to bore into undamaged fruit that is still in the process of ripening (unlike most fruit flies, which only lay their eggs in rotting or injured fruit that farmers don’t want anyway). By colonizing these fruits with their larvae, D. suzukii became the bane of cultivators of cherries, grapes and other fruits.

A closely related species to D. suzukii, Drosphila subpulchrella, also has a serrated ovipositor. With the help of undergraduate students in the Kopp lab, Lisa Teixeira, Raul Salazar and George Zaragoza, I investigated whether D. subpulchrella can also colonize ripening fruit, (and hence whether it is a potential pest) and compared its ability to do so with related species with nonserrated ovipositors. This system can also be analyzed from the perspective of evolutionary developmental biology: What changes in ovipositor development led to the evolution of the elongated, serrated form?

The origin of natural patterns: Sex combs galore

Differences between close relatives are often specific to one sex. For example, many male Drosophila flies have unusual bristle patterns on their first two legs. Female fly forelegs, on the other hand, are largely similar. These patterns are species-specific and remarkably diverse.

While most of us would not think twice about a fly’s legs, we may have often wondered about the origin of patterns in nature, like the designs on sea shells or the stripes on a zebra. Since flies have been well-studied genetically, philosophers and scientists have long used fly bristles to understand the genetics of pattern formation

In the Larsen lab at the University of Toronto, and later in the Kopp lab, I analyzed sex comb genetics, development and evolution. I found that male bristle patterns are the outcome of a complex process of cell rearrangement that modifies a standard female-like leg pattern into a male one. Across species, remarkably similar patterns often form through different developmental mechanisms.

Genetic analysis and characterization of the chromosome 22q11.2 deletion in affected children

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a complex set of medical and psychological symptoms, including a 25-30 fold increased risk for schizophrenia. 22q11.2DS commonly arises from an approximately 3 Mb haploid deletion on the long arm of chromosome 22. The size of this deletion can vary from child to child. Allelic variation of remaining gene copies corresponding to those in the deleted region may contribute to presentation and penetration of morphological and/or psychological symptoms.

We will use existing blood and saliva samples from children with 22q11.2DS to better characterize the extent of the deletion, degree of mosaicism, and the allelic variation of non-deleted copies of genes (COMT, PRODH) in the deleted region.

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