In our laboratory we are interested in using genomic technology to address several fundamental biological questions.
What is the set of genes found in the fungi?
The starting point for this work is the complete sequence of the genome of the yeast Saccharomyces cerevisiae. When the sequence of this genome became available at the end of 1996 it became clear that the genome of this yeast encodes about 6000 genes. While many groups are studying this particular research strain to learn more about basic fungal biology we are taking a somewhat different approach. By characterizing the genomes of related organisms starting with the filamentous fungus Ashbya gossypii we hope to more precisely define what are the set of genes in S. cerevisiae as well as to identify genes found in related fungi that have been lost from the genome of this yeast. Considerably more than 90% of the genes found in S. cerevisiae are found in Ashbya gossypii and likewise well over 90% of the genes found in Ashbya gossypiiare found in S. cerevisiae. This suggests that the set of genes found in this family of fungi is somewhat larger than the set of genes found in the standard research yeast, but not by very much.
How much genetic variation is there within a fungal pathogen species?
Our interest in this human pathogen is to expand beyond looking at one isolate and to investigate the diversity in the population. Are there genes found in some Cryptococcus neoformans isolates but not in others? Are there regions of the genome or individual genes which are highly diverged between Cryptococcus isolates? Efforts are now underway at Stanford University to sequence the genome of the JEC21 strain of Cryptococcus. This is a strain that has been agreed upon by the community of Cryptococcus researchers as a reference strain. But how much do other Cryptococcus isolates differ from JEC21?
What is the set of genes in humans?
The complete DNA sequence of human and mouse will become available soon. This does not mean that we will know the complete set of human or mouse genes. Our current state of knowledge does not allow us to accurately predict human genes directly from DNA sequence. We are interested in applying to the human genome some of the experimental and bioinformatic tools we are developing and utilizing in fungal systems.
We are currently establishing a high throughput sequencing and bioinformatics capacity to address the above questions.