INNOVATIVE CELL BIOLOGY AND
IMMUNOLOGY
SEMINAR GROUPS
ESCAPE ROOM
Enter the building
1) Discovery Lead (E)
2) Lead optimization (N)
3) Pre-clinics (T)
4) Phase I (R)
5) Phase II (A)
6) Phase III (N)
7) Submission (C)
8) Patients market (E)
Code: entrance
Inside the building
1) Corrosive
2) Oxidizing
3) Flammable
4) Explosive
Code: COFE
Models
a) Cell line model
- Particularly valuable for investigating pathophysiology and screening for
potential therapeutic targets of a variety of diseases and disorders in
biological systems
- Advantages
o Consistent
o Long life span
o Available in large quantities
o Cost-effective
o Have been used for a long time in research
b) Animal model
- Use of animal models in research resulted in the advancement of
knowledge for how diseases affect animal and humans
- It has also led to the effective treatment of many diseases
- Advantages
o Large number of offspring
o Lowers over-all cost of drug development
o In vivo model
o Possibility to do inheritance studies
c) Human model
- Human tissue is directly isolated from the tumour and retains the
morphological and functional characteristics of their tissues of origin
, - Advantages
o No inter-species differences
o Mimics in vivo tissues of interest
o Genetically stable
o Maintains original phenotype
We will start with research on an animal model, because this is easier to
translate to humans than cell line models (In vivo model). You can also do
inheritance studies with the offspring (which are plentiful).
- Major limitation of animal models: difficult to translate to human situation
Ethical approval
All animal research starts with getting approval of the Animal Welfare Body (IvD,
instantie voor dierenwelzijn). The animal welfare body determines whether the
importance of the animal experiment outweighs the use and additional
discomfort of the laboratory animals. As part of the approval procedure, prior to
the experiment you have to estimate the discomfort of the animals during the
entire experiment. Examples of discomfort ranging form mild to terminal are:
1. Spontaneous induction of a small, non-invasive tumor
2. Induction of a tumor that will disturb normal behaviour (but not cause
pain)
3. Induction of a metastatic melanoma that might cause some pain (but you
will inject painkillers)
4. Induction of a metastatic melanoma that likely cause pain and even death
Experimental approach
Once the IvD approves your experimental design, you can start your experiment.
There are many strategies to find targets for therapy using animal models, which
are listed below.
a) Implantation of human melanoma cells in mouse skin to analyze which
ones will metastasize. Combine with RNA sequencing on the tumor
material to identify genes that are involved in melanoma metastasis.
b) Use a CRISPR-CAS9 to mutate B16 cells and inject those in your host
mouse skin to analyze which ones will metastasize. Isolate the primary
tumors and metastasis and perform RNA sequencing to identify genes
related to metastasis.
c) In literature you find an interesting gene that is involved in colon cancer
metastasis and might therefore play a role in melanoma metastasis as
well. Knock this gene out in the B16 melanoma cell line and inject the cells
in your host mouse skin to analyse the effect of the knock down on
metastasis.
d) You choose to find stromal genes that promote metastatic niche
formation. Therefore you inject regular B16 melanoma cells in mice with
different genetic background
e) You induce melanoma using UV radiation and analyze which mutations
cause malignant transformation of melanoma
Lead 1
You received some primary melanoma cell lines from the clinic. You want to
inject the cells in a mouse model to compare their ability to metastasize. This
way you may find a protein that is correlated to melanoma metastasis and may
thus be a good target for your potential therapy.
Which mouse strain would you like to inject your cells in?
a) C57BL/6J mice
IMMUNOLOGY
SEMINAR GROUPS
ESCAPE ROOM
Enter the building
1) Discovery Lead (E)
2) Lead optimization (N)
3) Pre-clinics (T)
4) Phase I (R)
5) Phase II (A)
6) Phase III (N)
7) Submission (C)
8) Patients market (E)
Code: entrance
Inside the building
1) Corrosive
2) Oxidizing
3) Flammable
4) Explosive
Code: COFE
Models
a) Cell line model
- Particularly valuable for investigating pathophysiology and screening for
potential therapeutic targets of a variety of diseases and disorders in
biological systems
- Advantages
o Consistent
o Long life span
o Available in large quantities
o Cost-effective
o Have been used for a long time in research
b) Animal model
- Use of animal models in research resulted in the advancement of
knowledge for how diseases affect animal and humans
- It has also led to the effective treatment of many diseases
- Advantages
o Large number of offspring
o Lowers over-all cost of drug development
o In vivo model
o Possibility to do inheritance studies
c) Human model
- Human tissue is directly isolated from the tumour and retains the
morphological and functional characteristics of their tissues of origin
, - Advantages
o No inter-species differences
o Mimics in vivo tissues of interest
o Genetically stable
o Maintains original phenotype
We will start with research on an animal model, because this is easier to
translate to humans than cell line models (In vivo model). You can also do
inheritance studies with the offspring (which are plentiful).
- Major limitation of animal models: difficult to translate to human situation
Ethical approval
All animal research starts with getting approval of the Animal Welfare Body (IvD,
instantie voor dierenwelzijn). The animal welfare body determines whether the
importance of the animal experiment outweighs the use and additional
discomfort of the laboratory animals. As part of the approval procedure, prior to
the experiment you have to estimate the discomfort of the animals during the
entire experiment. Examples of discomfort ranging form mild to terminal are:
1. Spontaneous induction of a small, non-invasive tumor
2. Induction of a tumor that will disturb normal behaviour (but not cause
pain)
3. Induction of a metastatic melanoma that might cause some pain (but you
will inject painkillers)
4. Induction of a metastatic melanoma that likely cause pain and even death
Experimental approach
Once the IvD approves your experimental design, you can start your experiment.
There are many strategies to find targets for therapy using animal models, which
are listed below.
a) Implantation of human melanoma cells in mouse skin to analyze which
ones will metastasize. Combine with RNA sequencing on the tumor
material to identify genes that are involved in melanoma metastasis.
b) Use a CRISPR-CAS9 to mutate B16 cells and inject those in your host
mouse skin to analyze which ones will metastasize. Isolate the primary
tumors and metastasis and perform RNA sequencing to identify genes
related to metastasis.
c) In literature you find an interesting gene that is involved in colon cancer
metastasis and might therefore play a role in melanoma metastasis as
well. Knock this gene out in the B16 melanoma cell line and inject the cells
in your host mouse skin to analyse the effect of the knock down on
metastasis.
d) You choose to find stromal genes that promote metastatic niche
formation. Therefore you inject regular B16 melanoma cells in mice with
different genetic background
e) You induce melanoma using UV radiation and analyze which mutations
cause malignant transformation of melanoma
Lead 1
You received some primary melanoma cell lines from the clinic. You want to
inject the cells in a mouse model to compare their ability to metastasize. This
way you may find a protein that is correlated to melanoma metastasis and may
thus be a good target for your potential therapy.
Which mouse strain would you like to inject your cells in?
a) C57BL/6J mice
