Min-Hao Kuo Research Interests
1. Chromatin dynamics and regulation of nuclear activities.
Chromatin is a dynamic structure that not only organizes the genome, but also contributes significantly to the regulation and execution of a variety of nuclear activities, including cell cycle control and transcriptional regulation.
Faithful segregation of the duplicated genomes requires that both sister kinetochores are attached to mitotic spindles emanating from opposite spindle poles. Bipolar attachment results in physical tension between sister chromatids. 
Cells monitor the status of tension as a means to detect any mistake in kinetochore attachment. Uncorrected attachment errors may lead to missegregation and aneuploidy, a condition frequently linked to cancer. If missegregation occurs during meiosis, trisomy results, causing miscarriage and certain congenital diseases such as Down's syndromes. Spindle assembly checkpoint is the major safety control employed by all eukaryotes to ensure bipolar attachment. Our main research goals are to understand whether and how chromatin plays regulatory and/or structural roles in facilitating mitotic fidelity and progression. Currently, we focus on one histone H3 mutation, which impairs cellular ability to detect defects in sister chromatid tension and to activate the spindle assembly checkpoint when such tension sensing defects occur. Genetic and biochemical approaches are employed for functional and structural studies.
Histone H3 phosphorylation is conserved through evolution and has been used widely as a marker for mitosis progression. However, molecular functions exerted by the phosphorylated H3 remain elusive. Multiple residues within the amino terminal tail domain of H3 can be phosphorylated, singly or in different combination. We use genetic approach to dissect the functions of these different H3 modification events.
2. Post-translational modifications and protein functions.
Post-translational modifications (PTM) are chemical changes made to proteins after they are synthesized. PTMs may alter the underlying protein's structure, function, and ability to interact with other proteins, metabolites, or biomolecules.
Thus, the repertoire of proteome expands drastically when PTMs are considered. In fact, PTMs are essential and integral components of comprehensive proteomes.
A. In the Tumor suppressor p53 project, we combine biochemical and molecular biology approaches to studying how the structure and the transcriptional regulator functions of a tumor suppressor protein p53 is modulated by PTMs, including acetylation at its carboxyl terminus, as well as by phosphorylation at both the amino and the carboxyl termini. We hope to obtain a biochemical understanding on how p53 modifications may be linked to suppressing tumorigenesis.
B. We also are interested in other PTM-related functions. Continuing our interest in devising biotechnological tools for PTM research (e.g. the Tethered Catalysis/Yeast Two-Hybrid system, TC/Y2H, patented), we are developing a novel system by which we can obtain quantitatively modified proteins for in vitro biochemical studies. In addition to its biotechnological applications, we will use this system in our functional and biochemical studies of p53 and chromatin components, especially histones.
3. Lipid metabolism in a model microalga, Chlamydomonas reinhardtii.
The third-generation biofuel production focuses on using microalgae as the vehicle for biofuel production. Chlamydomonas reinhardtii is a model photosynthetic microalgae with which basic research on lipid metabolism can be applied to other microalgae for biofuel production. Using our expertise and experiences on yeast genetics, biochemistry, and molecular biology, we collaborate with Dr. Christoph Benning to identify means of increasing the lipid content of Chlamydomonas reinhardtii. In addition, we also collaborate with Dr. Barry William's group to use evolutionary approach to create yeast strains that are able to express higher amounts of lipids that might be suitable for biofuel use.