Download Network Dynamics of Budding Yeast Cell Cycle

Network Dynamics of
Budding Yeast Cell Cycle
Supervisor: Dr. Lei-han Tang
Presented by Cai Chunhui
April 16, 2005
Presentation Outline
 Introduction to budding yeast cell cycle
 Budding Yeast Cell Cycle Control
 Tang Chao’s model
 Transcriptional regulation network
 Further work
Introduction
• Yeast Cell Cycle
 G1:Cell grows and enter the
cell cycle
 S: Bud emerges and cell
duplicate its DNA
 G2: Preparation for mitosis
 M: Replicated DNA is
segregated into mother cell and
daughter cell.
Yeast Cell Cycle Control
• Yeast Cell Cycle is tightly regulated by cell cycle
control system
 A clock, or timer, that turns on each event at a specific
time, and provide a relatively fixed amount of time for
the completion of each event;
 A mechanism for initiating events in correct order;
 A mechanism to ensure that each event is triggered
only once per cycle;
 Binary (on/off) switch that trigger events in a complete,
irreversible fashion;
 Robustness, backup mechanism;
 Adaptability.
Yeast Cell Cycle Control
• Yeast Cell-cycle Control System is based on
 The activity of the cyclin-dependent kinase (CDK)
Cdc28.
 Gene regulation.
Yeast Cell Cycle Control
• Much is known about
Ccd28 activities and it
function when
associated with
different cyclins.
---- i.e. Cln2/Cdc28,
Clb5/Cdc28, Clb2/Cdc28.
MPF
synthesis
degradation
degradation
synthesis
SPF
Yeast Cell Cycle Control
• Gene Regulation is
poorly understand
-- ~800 out of 6126
genes oscillate
during cell cycle, with
unknown functions of
most genes
Yeast Cell Cycle Control
• Literature Database and source:
 http://genome-www5.stanford.edu/
 http://www.yeastgenome.org/
 http://web.wi.mit.edu/young/cellcycle/
 http://www.genome.jp/kegg/
Yeast Cell Cycle Control
• Time course data is combined with Richard
Young’s cell cycle data to have 792 cell cycle
genes.
• Gene expression data was normalized so that the
average log2(ratio) over the course of the
experiment is equal to 0 and further divided by
standard deviation.
Yeast Cell Cycle Control
• Gene expression
Yeast Cell Cycle Control
• Gene expression data testing
– Method: Fourier Transform
Im= ∑sin(ωtj)x(tj)
Re = ∑cos(ωtj)x(tj)
I = A2 + B2
Φ= tan-1(Im/Re)
where ω=2*π/T
(1)
(2)
(3)
(4)
Yeast Cell Cycle Control
Yeast Cell Cycle Control
• Result of data testing
– Similar periodical property
• Sorting
– Fourier Transform magnitudes
– Phase (time of peak expression)
Yeast Cell Cycle Control
Yeast Cell Cycle Control
Yeast Cell Cycle Control
g1
m/g1
s
g2/m
Yeast Cell Cycle Control
Orf
Phase
Orf
Phase
Orf
Phase
YPL187W'
'm/g1'
'YJL078C'
'g1'
'YBR009C'
's'
'YJL159W'
'm/g1'
'YJL115W'
'g1'
'YDR224C'
's'
'YKL185W'
'm/g1'
'YPL267W'
'g1'
'YBR010W'
's'
'YKL164C'
'm/g1'
'YBL035C'
'g1'
'YBL003C'
's'
'YKL163W'
'm/g1'
'YLR286C'
'g1'
'YMR003W'
's/g2'
'YDR261C'
's'
'YDR097C'
'g1'
'YML052W'
'g2/m'
'YOR307C'
'g1'
'YGR189C'
'g1'
'YHL028W'
'g2/m'
'YLR079W'
'm/g1'
'YIL066C'
'g1'
'YPR149W'
'g2/m'
'YKR077W'
'g1'
'YBR088C'
'g1'
'YMR032W'
'g2/m'
'YBR158W'
'm/g1'
'YDL003W'
'g1'
'YLR190W'
'g2/m'
'YOR308C'
'g1'
'YHR143W'
'g1'
'YBR038W'
'g2/m'
'YNL327W'
'm/g1'
'YAR007C'
'g1'
'YBR092C'
'g2/m'
'YBR108W'
'g1'
'YBR089W'
'g1'
'YDR033W'
'g2/m'
'YLR049C'
'g1'
'YOL090W'
'g1'
'YDR225W'
's'
'YGL028C'
'g1'
'YPL256C'
'g1'
'YBR054W'
'g2/m'
'YGR044C'
'g1'
'YOL007C'
'g1'
'YNL160W'
'm/g1'
'YCL024W'
'g1'
'YNL030W'
's'
Yeast Cell Cycle Control
Yeast Cell Cycle Control
• Genes are regulated in a periodic manner
coincident with the cell cycle.
• Such regulation is required for proper
functioning of the control mechanism to maintain
events’ order during cell cycle.
Yeast Cell Cycle Model
• How do physicists study
regulatory process of cell
cycle?
– To implement the yeast cell
cycle with the most
simplified network.
Yeast Cell Cycle Model
The network was simplified with the
components having just on-off
characteristics.
Thus, in the model each node only has
two states, Si=1(active state) and
Si=0(inactive state), with total 11 nodes.
1
0
Yeast Cell Cycle Model
The protein states propagation rule:
Yeast Cell Cycle Model
Fixed Points
Yeast Cell Cycle Model
Biological Pathway
Temporal evolution of protein states for the cell-cycle network
Yeast Cell Cycle Model
• Conclusion:
---- High stability and robustness
---- More stable with more components involved
Transcriptional Regulatory Network
• Cell cycle regulation
program is mainly due
to gene expression.
• Gene activation and
repression is via the
transcription of
sequence-specific
DNA-binding
transcription factors.
Transcriptional Regulatory Network
• The yeast cell cycle gene
expression program is
regulated by nine known
cell cycle transcriptional
factors. These cell cycle
transcription factors each
regulates a group of
genes, function during
one stage of the cell cycle
Transcriptional Regulatory Network
Transcriptional Regulatory Network
• Genomic analysis of regulatory network
dynamics reveals large topological
changes(Nature,2004)
NICHOLAS M. LUSCOMBE, M. MADAN BABU,
HAIYUAN YU, MICHAEL SNYDER,
SARAH A. TEICHMANN & MARK GERSTEIN
• http://sandy.topnet.gersteinlab.org/
– 409 out of 792 cell cycle genes involved in
3459 genes that constitute the yeast genome
network.
Transcriptional Regulatory Network
• G1/S:
Mbp1(YDL056W)
Swi4(YER111C)
Swi6(YLR182W)
Transcriptional Regulatory Network
• G2/M:
Fkh2(YNL068C)
Ndd1(YOR372C)
Mcm1(YMR043W)
Transcriptional Regulatory Network
• M/G1:
Mcm1(YMR043W)
Swi5(YDR146C)
Ace2(YLR131C)
Transcriptional Regulatory Network
Transcriptional Regulatory Network
• G1/S:
Mbp1(YDL056W)
Swi6(YLR182W)
Swi4(YER111C)
Transcriptional Regulatory Network
• Single transcription factor
– Fraenkel Lab - Yeast regulatory map
Transcriptional Regulatory Network
• G1/S:
Mbp1(YDL056W)
Swi6(YLR182W)
Swi4(YER111C)
Transcriptional Regulatory Network
• Three transcription factors (AND logic)
– Fraenkel Lab - Yeast regulatory map
Transcriptional Regulatory Network
• G1/S:
Mbp1(YDL056W)
Swi6(YLR182W)
Swi4(YER111C)
Transcriptional Regulatory Network
• Two transcription factors (OR logic)
– Fraenkel Lab - Yeast regulatory map
Further Work
• Combining expression data and binding
data to find gene regulatory network
• Find logic control between TF and genes,
especially combinatorial control
(AND,OR,NOR,NAND,XOR)
• Build a dynamic model.
Acknowledgement
• Supervisor
– Dr. Lei-han Tang
• Team member
– Hui Sheng
– Liang Shenghua
– Wang Chao