Yeast Yuanliang ZHAI
In the limited space of the eukaryotic nucleus, genes and chromosomes occupy preferential territories in a non-random manner and this location is increasingly recognized to affect gene expression, DNA replication and chromosome dynamics. There is considerable evidence that DNA replication and transcription do not occur diffusely throughout the nucleus, but rather at a number of discrete foci termed “factories” in which relevant inter- and intra-subchromosomal regions are clustered with pools of concentrated enzymatic factors required for DNA and RNA metabolism. The positioning of these foci closely correlates with local chromatin organization. Specifically, early replicating regions of the genome generally take an open, euchromatic conformation associated with highly active transcription. These regions localize to the nuclear interior. By contrast, late replicating heterochromatic domains with less active transcription localize largely at nuclear periphery or around the nucleolus. It has long been known that replication timing is intimately correlated with transcriptional competence of local chromatin domains. However, the underlying mechanism by which this function is linked to higher order of chromatin organization is poorly understood. As the entire yeast nucleus is a mere 1.5 µm in diameter, labeling proteins of the DNA replication complex combined with super-resolution microscopy offer the opportunity to view the fine details of the interactions of these proteins in time and in space as they interact with the DNA and with the various structures of the nucleus.
Mitochondrion and Parkinson’s disease Xiaoxuan Qu
Mitochondrion is an important double membrane organelle in eukaryotic cells and its major function is to supply energy in the form of adenosine triphosphate (ATP). The normal function of mitochondria is maintained by a dynamic fusion and fission processes to ensure damaged or abnormal mitochondria are removed through a process designated as mitophagy. Dysfunction of these processes is detrimental to the cell and has been linked to a number of diseases. For instance, Parkinson’s disease (PD) is a common neurodegenerative disorder which affects the movement of patients. The disorder is caused by the degeneration of a specific group of dopmainergic neurons in the substantia nigra pars compacta (SNc). The mechanism of why this group of neurons is affected is not completely known but dysfunction of mitochondrial dynamics and mitophagy have been suggested to be the major contributor for the pathogenesis of PD. For examples, PD patients have been consistently reported to have mitochondrial dysfunction in the cells and mutations in proteins such as parkin or PINK1 have been shown to associate with the development of familial PD and disruption of normal mitochondrial dynamics. The primary goal of our research is to study the mechanism of damaged mitochondria clearance and how dysfunction of this process can contribute to PD.
C. elegans HO YI MAK
Our long-term goal is to understand how fat storage is regulated at the endoplasmic reticulum (ER)-lipid droplets (LD) interface. We have previously shown that physical and functional coupling of LDs to the ER is facilitated by a macro-molecular complex and requires an intact tubular ER network. Using super-resolution microscopy, we will probe the localization of ER and lipid droplet marker proteins to define sub-domains of these organelles that are pertinent to fat storage.