Here are some of the projects I am working on:

1. Regulation of Olig2expression
  

Olig 2 is involved in generating oligodendrocytes. Oligodendrocytes are vital to vertebrates since they are essential in maintaining the myelin sheaths, which allows faster signal conduction. Myelin sheaths are unique to vertebrates. Invertebrates, such as squid and octopus, do have nerves but not meylin sheaths. Studies have shown that Olig2 is expressed in differentiated ES cells but not in undifferentiated cells. What makes studying Olig2 attractive, besides it is an important gene, is that it is regulated at the transcriptional level. Our hypothesis is that some of the non-coding sequences upstream of Olig2 are involved in its regulation. Dr. Gottlieb's lab has developed a in vivo system in which the genomic region around Olig2 is cloned into a 220KB BAC and the Olig2 gene is replaced with luciferase. We are currently collaborating with Dr. Gottlibe's lab to identify potential targets that regulate Olig2 gene expression.

2. The tale of Ultraconserved Elements
  

Several recent computational studies identified segments of non-coding DNA that are more conserved than coding sequences across many species, such as human, mouse and rat [1-6]. "Ultraconserved elements", an extreme example of these segments, are defined as regions of DNA that are 100% identical across the human, mouse and rat genomes. Some of these elements are even conserved in the chicken, dog and puffer fish genomes [1, 2]. An intriguing observation is that some ultraconserved elements show high similarity with each other, forming clusters[1, 2]. These elements are perfectly conserved in different species, yet diverge within the same species. A possible scenario is that a gene duplication event had occurred prior to speciation, creating two copies of the same sequence which diverged from each other and later became fixed. The functions of these sequences, if any, as well as the evolutionary forces preserving their sequence identity are currently unknown. The goal of this project is to gain insight into the functions of these highly conserved non-coding segments and the molecular and evolutionary mechanisms that maintain their high level of sequence identity.

Reference:

1. Bejerano, G., D. Haussler, and M. Blanchette, Into the heart of darkness: large-scale clustering of human non-coding DNA. Bioinformatics, 2004. 20 Suppl 1: p. I40-I48.
2. Bejerano, G., et al., Ultraconserved elements in the human genome. Science, 2004. 304(5675): p. 1321-5.
3. Dermitzakis, E.T., et al., Comparison of human chromosome 21 conserved nongenic sequences (CNGs) with the mouse and dog genomes shows that their selective constraint is independent of their genic environment. Genome Res, 2004. 14(5): p. 852-9.
4. Gaffney, D.J. and P.D. Keightley, Unexpected conserved non-coding DNA blocks in mammals. Trends Genet, 2004. 20(8): p. 332-7.
5. Margulies, E.H., et al., Identification and characterization of multi-species conserved sequences. Genome Res, 2003. 13(12): p. 2507-18.
6. Thomas, J.W., et al., Comparative analyses of multi-species sequences from targeted genomic regions. Nature, 2003. 424(6950): p. 788-93.
7. Jaillon, O., et al., Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature, 2004. 431(7011): p. 946-57.


3. Analysis of Gene expression data
  

Since its invention, microarray technology has been used frequently in assessing global gene expression under certain conditions or to compare the differences between gene expressions under two or more conditions. Several approaches have been advocated in analysizing the gene expression: clustering, analysis of variance (ANOVA), regression and etc. We believe that the ANOVA approach is more useful in extracting the information we want from different yeast strain experiments and have looked into the strengths of different ANOVA models in hope to construct one that best suited our objectives.