Professional Documents
Culture Documents
Biology
Prepared by:
Dr. H. Yohannes Alen, MSc.
Pharmaceutical Sciences
Andalas University
Indonesia
Databases
Kyoto Encyclopedia of Genes and Genomes
Alliance for Cellular Signaling
Signal Transduction Knowledge Environment
p53
Protein 53
Produces 53 proteins kiloDaltons
Guardian of the genome
Detects DNA damages
Halts the cell cycle if damage is detected
to give DNA time to repair itself
p53
If (damage equals true and repairable = true)
halt cell cycle
else
if(damage equals true and repairable = false)
induce apoptosis (suicide)
ataxiatelangiectasiamutated
p53
p53
activates
p21
deactivates
No cell cycle!
CDK
p53
Cancer Drugs
Alkylating agents - interfere with cell division and affect the cancer
cells in all phases of their life cycle. They confuse the DNA by
directly reacting with it.
Antimetabolites - interfere with the cell's ability for normal
metabolism. They either give the cells wrong information or block
the formation of "building block" chemical reactions one phase of
the cell's life cycle.
Vinca alkaloids - (plant alkaloids) are naturally-occurring chemicals
that stop cell division in a specific phase.
Taxanes - are derived from natural substances in yew trees. They
disrupt a network inside cancer cells that is needed for the cells to
divide and grow.
all inhibit the cell cycle
Advantages of Computational
Systems Biology
It is highly relevant in discovering more
complex relationships involving multiple
genes
This may create new opportunities for
drug discovery
Better medical therapies for individual
treatments
Whats to come?
Current work is on small sub-networks
within cells.
Feedback circuit of bacteria chemotaxis
Circadian Rhythm
Parts of signal-transduction pathways
Simplified models of the cell cycle
Models of the Red blood cells
Whats to come?
Research has begun on larger-scale
simulations
Biochemical network level
Simulation of Epidermal Growth Factor (EGF)
signal-transduction cascade
The Physiome Project
Biochemical Networks
Problem:
The behavior of cells is governed and
coordinated by biochemical signaling networks
that translate external cues (hormones, growth
factors, stress, etc.) into adequate biological
responses such as cell proliferation,
specialization or death, and metabolic control.
Motivation:
Deep understanding of cell malfunction is crucial
for drug development and other therapies.
Available: [online]
http://www.brc.dcs.gla.ac.uk/projects/bp
s/bps_slides/bps_slides.pdf
Biochemical Networks
Biochemical Networks
Concurrency Theory
Concurrent, communicating systems have been the
subject of intense study by Computing Scientists. Rich
theories and tools have been developed to aid in design,
analysis and verification of such systems.
Concurrent systems are inherently complex. To manage
complexity, theories and tools have been developed to
allow programmers to simulate behaviour. Simulators
allow the analysis of traces through concurrent
executions and provide a testbed for experimentation.
At a more abstract level, temporal analysis involves
proving that a concurrent system adheres to a temporal
property, i. e. it can be shown that a network protocol
always delivers data packets in the same order they
were sent.
Concurrency
A concurrent system is one where multiple processes exist at the same time. These
processes execute in parallel and potentially interact with each other. As an example of a
concurrent system, consider an internet banking site. The server and multiple client
processes exist at the same time, with interactions occurring between the individual clients
and the server.
Concurrency in Biochemical
Networks
Biochemical networks are also concurrent communicating systems. Pathways consist of
sequences of interactions which sometimes affect other parallel pathways. As an
example, consider two pathways involved in cell division. The Ras- Raf pathway which
triggers the cell division and the PI- 3K- Akt pathway which keeps the cell alive are both
triggered by the same growth factor. The sequences of interactions in both pathways run
concurrently with some interaction i. e. Akt inhibits Raf.
Complex modeling of
concurrent systems
Asynchronous circuits have been used to
simplify circuit analysis
Perhaps they could be used to examining
concurrent biological systems.