Date :

 24, 27-28 July 2009

Place :

 24 July: Room 312, Department of Physics, National Taiwan University, Taipei

 27-28 July: the auditorium on 1st floor, Institute of Physics, Academia Sinica, Taipei

 National Center for Theoretical Sciences (Critical Phenomena and Complex Systems focus group)

 Institute of Physics, Academia Sinica (Taipei)

 Miss Chia-Chi Liu (Secretary, Physics Division, NCTS)
 Tel:(886)-2-33665566; Fax:(886)-2-33665565; E-mail: ccliu@phys.ntu.edu.tw

Speakers :

Dr. Yeng-Long Chen
Institute of Physics, Academia Sinica, TAIWAN
E-mail: yenglong@phys.sinica.edu.tw

Polymer Dynamics in the Micro- and Nano-scale: How Can Hydrodynamic Interactions Affect DNA Dynamics

Dr. Yun-Ru Chen
The Genomics Research Center, Academia Sinica, Taipei, TAIWAN
E-mail: yrchen@gate.sinica.edu.tw

Conformational Stability of Amyloid β Predominantly Determines the Nucleation Phase of Fibrillization

    The amyloidogenic protein, amyloid β peptide (Aβ) is the critical component of senile plaques found in the lesions of Alzheimer disease (AD) patients.  The progressive Aβ fibril formation due to Aβ aggregation is believed to be the causative factor of AD. Despite sporadic AD in which no mutation occurred, inheritable familial AD containing autosomal mutations in Aβ, for example: Flemish A21G, Dutch E22Q, Artic E22G, and Iowa D23N mutants causes early onset of AD.  These clinically relevant mutations heavily located at residue 21-23 in proximity of the turn region of Aβ. Emerged evidences showed that Aβ oligomers that formed within the aggregation process rather than the mature fibrils are the actual toxic entity.  This announces the importance of understanding the early stages of Aβ aggregation.  Since Aβ aggregation is a protein misfolding event, it is essential to understand its fundamental folding mechanism and the relationship between folding and aggregation. 

    Previously, we examined the equilibrium folding properties of Aβ40 and 42 and found their initial species and conformation stability are strikingly different [1]. Here, we further examine the equilibrium folding mechanisms of the familial Aβ40 mutants and link their property with the fibrillization process [2]. By using far UV circular dichroism and BisANS fluorescence, we found that all Aβ mutants have similar residual secondary structures, but distinct surface-exposed hydrophobic clusters. All Aβ40 mutants are monomeric revealed by analytical ultracentrifugation and native PAGE. The GdnHCl denaturation study shows that they adopt two-state folding mechanism but have significant difference in their Gibbs free energy. The order of the conformational stability is as such, A21G>WT> D23N >E22G=E22K=E22Q.  We found all E22 mutants and D23N are destabilized and do not fold reversibly like WT and A21G. The fibrillization study using thioflavin T assay shows that the more stable the species and slower the fibrillization except D23N. Moreover, we found the decrease of the native Aβ fold leads to decrease of fibril formation but increase of amorphous aggregates. Overall, we demonstrate that conformational stability and the native fold are important determinants for amyloid β fibrillization.

Reference

[1] Chen, Y.R. & Glabe, C.G. Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42. J Biol Chem 281, 24414-22 (2006).

[2] Chun-Lun Ni, Hoi-Ping Shi, Yu-Jen Chang, Guo-Ging Lin, Hui-Mei Yu, and Yun-Ru Chen. Conformational Stability and the Native Fold are Important Determinants for Amyloid beta Fibrillization. (2009). In Preparation.

Dr. Tzyy-Jen Chiou

Agricultural Biotechnology Research Center, Academia Sinica, TAIWAN

E-mail: tjchiou@gate.sinica.edu.tw

The Role of microRNA in Sensing Nutrient Stress in Plants

Prof. Jonathan Dushoff

Department of biology, McMaster University, CANADA

E-mail: dushoff@mcmaster.ca

1. Models of Infectious Disease Dynamics

2. Interventions Against HIV

3. Estimating Epidemic Spread from Data

4. Molecular Evolution of Influenza A

Dr. Shura Hayryan

Institute of Physics, Academia Sinica, TAIWAN

E-mail: shura@phys.sinica.edu.tw

1. Why Single-Stranded RNA Do Not Form Parallel-Strand Duplex?

    We study several properties of RNA-like molecule using Monte-Carlo simulations on cubic lattice. The influence of the secondary and tertiary interactions on the collapse transition is examined. We investigate formation of the parallel and anti-parallel duplexes, and show that anti-parallel duplex formation is entropically favourable in comparison with parallel one. The possible evolutionary implications are discussed.

2. A Worldwide Accessible Database of Structures and Thermodynamic Properties of micorRNA

    In this project we study systematically the structure and thermodynamic properties of thousands of microRNAs. By performing replica exchange Monte Carlo technique we obtain temperature dependencies of thermodynamic parameters for miRNAs and the lowest free energy conformation which is biologically active. Over 4000 miRNA sequences have been simulated so far. The results of our calculations will be organized as relational database and posted on internet for free usage.  

Prof. Meiying Hou

Institute of Physics, Chinese Academy of Sciences, CHINA

Email: mayhou@aphy.iphy.ac.cn

Velocity Distribution of Granular Gases

Prof. Chin-Kun Hu

Institute of Physics, Academia Sinica, TAIWAN
E-mail: huck@phys.sinica.edu.tw

Simple models of Protein Aggregation

Dr. Yuk-Gyn Joanna Lau

Institute of Physics, Academia Sinica, TAIWAN

E-mail: yglau@phys.sinica.edu.tw

DNA Dynamics on Lipid Membranes

Prof. D. Y. Lando

Belarus National Academy of Sciences, BELARUS

E-mail: lando@phys.sinica.edu.tw

Thermodynamic Properties DNA with Strands Crosslinked by Antitumor Compounds

Dr. Wen-Jong Ma

Institute of Physics, Academia Sinica, TAIWAN

E-mail: mwj@gate.sinica.edu.tw

Regions of Possible Aftershock Can Be Identified by Using Correlation Matrix for Earthquakes

    Finding the patterns of collective activities from data of time sequences is very useful in revealing the underlying structure or dynamics of complex systems. Such an approach is particularly valuable in the study of earthquakes, for which the mechanisms and the physical conditions over a long time or a global spatial scale, are beyond the control of a bottom-up approach. Here, we study the sequences of energy releases in the Taiwan region after dividing the region into cells of equal area.  We reveal the patterns of cell-to-cell correlations via a
 {\it correlation matrix approach}. The analysis of the full random counterpart of such time sequences clearly identifies cross correlations as they emerge from the random background. From the eigenvector corresponding to the largest eigenvalue, we can locate intensively correlated regions in Taiwan. These correlations can provide the blueprint for a construction of a regional probability map of the aftershock occurrences after the main earthquakes.
　

Dr. Zindoga Mukandavire

Department of Public Health, China Medical University, TAIWAN

E-mail: zmukandavire@gmail.com

1. Modelling Male Circumcision as HIV/AIDS Preventive Strategy

    A mathematical model for heterosexual transmission of HIV/AIDS is proposed for modelling male circumcision as a preventive control strategy for HIV/AIDS.We determine and use the basic reproductive number for the model to assess the effectiveness of male circumcision in slowing or curtailing the epidemic.  The model is numerically analysed to assess the effects of male circumcision on the transmission dynamics of HIV/AIDS. We conclude from the study that in the continuing absence of a preventive vaccine or cure for HIV/AIDS, male circumcision is a potential preventive strategy of HIV/AIDS to help communities slow the development of HIV/AIDS epidemic.

2. The Effects of Homosexuals and Bisexuals on the Dynamics of HIV/AIDS in Heterosexual Settings

    A deterministic compartmental sex-structured HIV/AIDS model for assessing the effects of homosexuals and bisexuals on the dynamics of the disease in heterosexual settings in which homosexuality and bisexuality issues have remained taboo is presented. The epidemic threshold known as the basic reproductive number suggests that heterosexuality, homosexuality, and bisexuality influence the growth of the epidemic in HIV/AIDS affected populations and the partial reproductive number with the larger value influences the overall dynamics of the epidemic in a setting. Numerical simulations of the model show that as long as one of the partial reproductive numbers is greater than unity, the disease will exist in the population. We conclude from the study that homosexuality and bisexuality enlarge the epidemic in heterosexual setting. The theoretical study highlights the need to carry out substantial research to map the homosexuals and bisexuals as it has remained unclear as to what extent these groups have contributed to the epidemic in heterosexual settings especially in southern Africa, which has remained the epidemiological locus of the epidemic.

Prof. Ann-Ping Tsou

Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, TAIWAN

E-mail: aptsou@ym.edu.tw

microRNA122 in Liver Biology

Boolean Logic Model for Qualitative Modeling of Gene Regulatory Networks for Simulating and Designing with Metabolic Pathways in Lactococcus lactis

    Biological processes are largely controlled by regulatory networks, which involve various kinds of molecular interactions. Different mathematical approaches have been proposed to model such genetic networks and to simulate their dynamical behavior, ranging from quantitative formalisms (e.g. sets of differential or stochastic equations) to crude Boolean models. In many instances, in particular in the case of the study of gene regulatory networks, precise quantitative data are usually lacking. For this reason, we lean on a qualitative and flexible formalism. Although this formalism has proven its usefulness for the modeling of various genetic regulatory networks, it has seldom been linked with quantitative metabolic models. We propose to develop genetically- regulated metabolic models precisely to fulfill this gap. To illustrate the applicability of our genetically-regulated metabolic modeling, we will set up a preliminary model and experimental testing of the regulatory network involved in the definition of the defined pyruvate distribution metabolic module in the lactic acid bacterium Lactococcus lactis.  

    We construct Boolean model for the gene regulatory network. Its logic rule is based on the representation of the mRNA and protein level. The time profile of the gene expression network is governed by whether the components are provided and by the topology of the network.