Introduction to

Bioengineering (BBL1020)
Instructor: Dr. Dinesh K. Ahirwar
Department: Bioscience & Bioengineering
Lecture-19
30/09/2024
Storage of genetic information

central dogma of biology

cell division
inheritance

genetic variation
Scale up to production stage

Insulin

Scale up

Conceptualization
Ideation
Scale up to production stage

Divide

Growth signal
proteins

Building blocks
(Macromolecules)

Scale up

Conceptualization
Ideation
Scale up to production stage

Cell division

Identical cells
Importance of cell division
Importance of cell division
Repair

Defense

Growth
 Cell cycle and division

p53
Rb
P21

HHMI BioInteractive - Click and Learn - The Eukaryotic Cell Cycle and Cancer
Abnormal Abnormal
Immune Response cell division
Cell signaling
Neurogenesis
 Phases of the cell cycle
• Yeast cells divide in 90 minutes
r

1h
4h

r
• Embryo cells complete cell
cycle in 30 minutes
8
hr

hr
11
Stages of cell cycle
Mitosis leads to two identical daughter cells : is it always true?
An example of stem cells

Symmetric cell division Asymmetric cell division

S S S

S S D D D S

Self Maintenance / Self Renewal

S: Stem cell
Ability to produce other cell types via differentiation
D: Differentiated cell
Lung-on-chip
 Cell Cycle Control
Basic control system should possess the following features
A clock, or timer, that turns on each event at a specific time, thus providing a fixed amount of time for the
completion of each event.

A mechanism for initiating events in the correct order; entry into mitosis, for example, must always
come after DNA replication.

A mechanism to ensure that each event is triggered only once per cycle.

Binary (on/off) switches that trigger events in a complete, irreversible fashion.

Robustness: backup mechanisms to ensure the cycle can work properly even when parts of the
system malfunction.

Adaptability: so that the system's behavior can be modified to suit specific cell types or environmental
conditions.
Discovery of cell cycle regulators
• Inhibition of protein synthesis depicted that new proteins are required for
G2 – M transition
• Unfertilized and fertilized sea urchin eggs + radioactive methionine
• Cell extracts harvested at different time intervals were analyzed by gel
electrophoresis
• Periodic accumulation
and degradation of a
protein, he called it
cyclin
 Types of cyclins
1.G1/S-cyclins bind Cdks at the end of G1 and
commit the cell to DNA replication.

2.S-cyclins bind Cdks during S phase and are

required for the initiation of DNA replication.

3.M-cyclins promote the events of mitosis

4. In yeast cells, a single Cdk protein binds all

classes of cyclins and drives all cell-cycle events by
changing cyclin partners at different stages of the
cycle. In vertebrate cells, by contrast, there are four
Cdks. Two interact with G1-cyclins, one with G1/S-
and S-cyclins, and one with M-cyclins.
 Cyclin-Dependent Kinases (CDKs)
At the heart of the cell-cycle control system is a family of protein kinases known as cyclin-dependent
kinases (Cdks).

The activity of these kinases rises and falls as the cell progresses through the cycle. The oscillations
lead directly to cyclical changes in the phosphorylation of intracellular proteins that initiate or
regulate the major events of the cell cycle—DNA replication, mitosis, and cytokinesis.

Cyclical changes in Cdk activity are controlled by a complex array of enzymes and other proteins.
The most important of these Cdk regulators are proteins known as cyclins.

Cdks unless they are tightly bound to a cyclin, they have no protein kinase activity.

Cdk levels, by contrast, are constant, at least in the simplest cell cycles.

Cyclical changes in cyclin levels result in the cyclic assembly and activation of the cyclin-Cdk
complexes; this activation in turn triggers cell-cycle events.
Negative control of cell cycle
 Negative control in cell cycle progression
Negative regulators halt the cell cycle.

The best understood negative regulatory molecules are retinoblastoma protein (Rb), p53, and p21.

Rb, p53, and p21 act primarily at the G1 checkpoint.

p53 is a multi-functional protein that has a major impact on the cell’s commitment to division; it acts when
there is damaged DNA in cells that are undergoing the preparatory processes during G1. If damaged
DNA is detected, p53 halts the cell cycle and recruits enzymes to repair the DNA. If the DNA cannot be
repaired, p53 can trigger apoptosis (cell suicide) to prevent the duplication of damaged chromosomes.

As p53 levels rise, the production of p21 is triggered.

p21 enforces the halt in the cycle dictated by p53 by binding to and inhibiting the activity of the Cdk/cyclin
complexes. As a cell is exposed to more stress, higher levels of p53 and p21 accumulate, making it less
likely that the cell will move into the S phase.
P53

DNA damage
Peto’s Paradox - Why large animals do not have cancer ???
DNA replication
Synthesizes DNA
Joins DNA fragments

DNA ligase Single-strand DNA cut

Opens DNA