2.1 Romania
- In Romania, Alzheimer’s is often invisible until it is too late.
- Delayed diagnosis: families wait months for formal assessment.
- Stigma: dementia is often dismissed as “normal aging.”
- Care burden: most care is unpaid, straining families financially.
- Infrastructure: memory clinics are scarce and unevenly distributed.
8+ months: average wait for diagnosis.
35 hrs/week: unpaid caregiver time.
<15 clinics nationwide.
2.2 Worldwide
- In Romania, Alzheimer’s is often invisible until it is too late.
- Delayed diagnosis: families wait months for formal assessment.
- Stigma: dementia is often dismissed as “normal aging.”
- Care burden: most care is unpaid, straining families financially.
- Infrastructure: memory clinics are scarce and unevenly distributed.
88+ months: average wait for diagnosis.
355 hrs/week: unpaid caregiver time.
<155 clinics nationwide.
CONCLUSION
TIMELINE!
Current drug pipeline
Tau pathology correlates better with cognitive decline than amyloid.
Tau spreads via extracellular seeds and intracellular aggregates.
Conditional therapies
Current drugs: costly, limited effect, side effects.
Missing piece: therapies that only activate in disease states.
1. LOREM IPSUM1 LOREM IPSUM2 LOREM IPSUM3 .
Triple-input AND gate integrates oxidative, inflammatory, and mitochondrial stress.
Built with Cre recombinase inversion and Gal4-VP16 fusion.
Fires only when all three conditions are met.
Built with Cre recombinase inversion and Gal4-VP16 fusion.
Fires only when all three conditions are met.
2. LOREM IPSUM1 LOREM IPSUM2.
Optogenetic PP2A system.
Uses blue light to control tau dephosphorylation reversibly.
Provides reversible, precise control inside neurons.
Uses blue light to control tau dephosphorylation reversibly.
Provides reversible, precise control inside neurons.
3. LOREMIPSUM1LOREMPIPSUM2
Genetically encoded chimera with 3 parts:
Modular → domains can be swapped for other diseases. Visual: Card; animation shows chimera entering cell → lysosome.
- AT8 scFv → binds tau seeds.
- TfR-binding peptide → crosses blood–brain barrier.
- IGF2 dimer → routes to lysosomes.
Modular → domains can be swapped for other diseases. Visual: Card; animation shows chimera entering cell → lysosome.
1. Proteus targets genotypes rather than phenotypes.
Cancer resistance to treatment often develops in a similar way to antibiotic resistance: cancer cells
expressing
particular phenotypes survive treatment and replicate, creating treatment-resistance tumour masses. Because
Proteus targets cancer at the mRNA level instead of the expression level, it is capable of targeting cells
with
distinct and varied phenotypes as long as they have the same driver mutation: a gene often responsible for the
cancerous properties of the cell.
This approach is especially relevant for pancreatic cancer, where KRAS driver mutations consist of up to 95% of cases. KRAS is a protein that is critical for the regulation of cell signalling for mitosis and proliferation. Mutations in KRAS G12 lead to constitutive activation of the protein, a Ras GTPase. This signals the cell to divide constantly.
By using KRAS as our guideRNA (gRNA) we can target specific mutations that cause the cancerous property–in this case, constant division. We can cut to the genotype instead of targeting different traits the cell may express as other drugs do.
This approach is especially relevant for pancreatic cancer, where KRAS driver mutations consist of up to 95% of cases. KRAS is a protein that is critical for the regulation of cell signalling for mitosis and proliferation. Mutations in KRAS G12 lead to constitutive activation of the protein, a Ras GTPase. This signals the cell to divide constantly.
By using KRAS as our guideRNA (gRNA) we can target specific mutations that cause the cancerous property–in this case, constant division. We can cut to the genotype instead of targeting different traits the cell may express as other drugs do.
2. Pyroptosis recruits immune response.
Cancer often makes itself invisible to the immune system.
Pyroptosis triggers inflammatory cytokines, DAMPs
(damage-associated molecular patterns), immune factors
such as IL-1B and IL-18, and cells such as macrophages and
dendritic cells to the site of cell death. In contrast,
apoptosis–the typical avenue of cell death–releases
anti-inflammatory factors.
It is not possible to have 100% transfection rates with most therapeutic systems that exists today. This allows Proteus to trigger the immune system to destroy cancer cells in the surrounding area even if transfection rates are not 100%.
It is not possible to have 100% transfection rates with most therapeutic systems that exists today. This allows Proteus to trigger the immune system to destroy cancer cells in the surrounding area even if transfection rates are not 100%.
3. Proteus is highly modular.
Proteus can also be optimized to bind to other mutations
in a patient’s cancer profile, so it can be adapted even
if the patient does not have the KRAS mutation in their
tumour profile. To identify mutations in a cancer
patient’s profile that would be ideal to select as a gRNA,
we created a dry-lab tool that finds optimal targets for
the Proteus system.
In addition, our approach of targeting cancer driver mutations means that this therapeutic can be applied beyond pancreatic cancer. Proteus can target mutations in different cancers or perhaps even be used to target other genotype-driven diseases.
Proteus is also a synthetic biology tool. The fusion protein cleaved can be modified with the insertion of a different Csx30 linker. Our BioBricks leverage the modularity of the system, and we encourage other iGEM teams and researchers to imagine the possibilities of leveraging the Craspase system. We’re excited to see what you come up with.
In addition, our approach of targeting cancer driver mutations means that this therapeutic can be applied beyond pancreatic cancer. Proteus can target mutations in different cancers or perhaps even be used to target other genotype-driven diseases.
Proteus is also a synthetic biology tool. The fusion protein cleaved can be modified with the insertion of a different Csx30 linker. Our BioBricks leverage the modularity of the system, and we encourage other iGEM teams and researchers to imagine the possibilities of leveraging the Craspase system. We’re excited to see what you come up with.
4. Proteus is highly modular.
Proteus can also be optimized to bind to other mutations
in a patient’s cancer profile, so it can be adapted even
if the patient does not have the KRAS mutation in their
tumour profile. To identify mutations in a cancer
patient’s profile that would be ideal to select as a gRNA,
we created a dry-lab tool that finds optimal targets for
the Proteus system.
In addition, our approach of targeting cancer driver mutations means that this therapeutic can be applied beyond pancreatic cancer. Proteus can target mutations in different cancers or perhaps even be used to target other genotype-driven diseases.
Proteus is also a synthetic biology tool. The fusion protein cleaved can be modified with the insertion of a different Csx30 linker. Our BioBricks leverage the modularity of the system, and we encourage other iGEM teams and researchers to imagine the possibilities of leveraging the Craspase system. We’re excited to see what you come up with.
In addition, our approach of targeting cancer driver mutations means that this therapeutic can be applied beyond pancreatic cancer. Proteus can target mutations in different cancers or perhaps even be used to target other genotype-driven diseases.
Proteus is also a synthetic biology tool. The fusion protein cleaved can be modified with the insertion of a different Csx30 linker. Our BioBricks leverage the modularity of the system, and we encourage other iGEM teams and researchers to imagine the possibilities of leveraging the Craspase system. We’re excited to see what you come up with.
Explore our project.
