iGEM 2023 — Team paris-bettencourt

{% extends "layout.html" %}
{% block title %}Notebook{% endblock %}
{% block lead %}Document the dates you worked on your project. This should be a detailed account of the work done each day for your project.{% endblock %}
{% block page\_content %}

## What should this page contain?

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* Chronological notes of what your team is doing.
* Brief descriptions of daily important events.
* Pictures of your progress.
* Mention who participated in what task.

## Inspirations

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* [2018 Munich](http://2018.igem.org/Team%3AMunich/Notebook)
* [2019 Georgia State](https://2019.igem.org/Team%3AGeorgia_State/Notebook)
* [2019 Newcastle](https://2019.igem.org/Team%3ANewcastle/Notebook)
* [2020 IISER Pune India](https://2020.igem.org/Team%3AIISER-Pune-India/Notebook)
* [2020 Lund](https://2020.igem.org/Team%3ALund/Notebook)
* [2020 NOVA LxPortugal](https://2020.igem.org/Team%3ANOVA_LxPortugal/Notebook)
* [2020 RDFZ China](https://2020.igem.org/Team%3ARDFZ-China/NoteBook)

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{% extends "layout.html" %}
{% set page\_heading = 'Engineering Success' %}
{% set page\_subheading = 'Demonstrate engineering success in a part of your project by going through at least one iteration of the engineering design cycle.' %}
{% set layout\_section1 = 'Ideation' %}
{% set layout\_section\_description1 = 'Conceptual overview of the project idea' %}
{% set layout\_section2 = 'Experimental Pipeline' %}
{% set layout\_section\_description2 = 'Full scope of the experimental journey, in-silico and wet lab' %}
{% set layout\_section3 = 'Experiments' %}
{% set layout\_section\_description3 = 'Detailed explanation of experiments' %}
{% set layout\_section4 = 'Experiments' %}
{% set layout\_section\_description4 = 'Detailed explanation of experiments' %}
{% block sidebar\_content %}
- [Ideation](#section1)
- [Proof of Concept](#section2)
- [Model Target Identification](#section3)
  * [STIs](#section3.1)
- [RFdiffusion protein design and in-silico analysis](#section4)
- [Protein expression and purification](#section5)
- [Protein binding assessment](#section6)
- [Phage infectivity assays](#section7)
{% endblock %}
{% block page\_content %}

## Ideation

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Our design principle expands on the pre-existing virus-trapping capacities of the natural glycoprotein mucin. To facilitate this, we have conceptualised a two-way intermediary binding protein which acts as a glue, enhancing stickiness of the pathogen and mucin to each other. With the increase in particle size of pathogen-binder, or mucin-binder complexes through abundant binder proteins in the viscous solution, we hope to increase the diffusion coefficient of the particles such that even with non-permanent, transient binding between individual proteins, we can effectively immobilise and reduce the rate of cell entry of the pathogens.

By having a constant solid base made of the mucin binding protein (from those in nature) and a flexible linker which increases the binding range of the two domains, and a modularly interchangeable pathogen-binding domain, we hope to show that we can effectively and efficiently generate a library of binding proteins tailored to individual pathogens, potentially not limited by species, genus, or even domain of the pathogen.

## Proof of Concept

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For our proof of concept, we wanted to build test designs for two separate target pathogens. One to test our ability to bind and sequester capsid proteins from the human pathogen HPV. The second, to test our theory of reducing cell entry by pathogens, through the model of T4 phage into *E. coli.*

## What is sexual health?

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Our first human practice step was to develop a solid understanding of what  [sexual health](https://www.who.int/health-topics/sexual-health#tab=tab_1) is.

According to the WHO, health is as a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity. Sexual health is fundamental to overall health and well-being. It requires both:

* A positive and respectful approach to sexuality and sexual relationships
* The means and possibility of enjoying pleasurable and safe sexual experiences

Unfortunately, sexual health-related issues are  [wide-ranging](https://docs.google.com/document/d/1xUIJRc23R_vG6H_QgPldRAKaRgPS8tHVgg1OuwKDSZU/edit?usp=drive_link). These include the spread and prevalence of sexually transmitted infections (STIs)

The  [WHO global health sector strategies on HIV](https://www.who.int/publications/i/item/9789240053779), viral hepatitis and sexually transmitted infections clearly states that ending sexually transmitted epidemics by 2030 will require:

* Massively scaling up primary prevention
* Increasing access to screening
* Raising awareness of the public health impact of STIs
* Securing adequate funding

Because sexual health has been so little explored as a concept by past iGEMers, you can find our complete and exhaustive introduction to the topic here.

### An introduction to STIs

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* A mucin-based lubricant backbone
* Central modular binding proteins containing:

+ Universal mucin-binding domain, based on mucin dye StcEE447D
+ Unique target-binding domain, designed through RFdiffusion
+ Flexible linker to increase binding domain availability

## What exact problem do we want to address?

---

While scientific publications and white papers gave us key broad insights to the field, it was crucial for us to get in contact with patients, governmental and non-governmental organisations to understand what STIs meant in terms of lived experience and current challenges.

Our bodies naturally produce mucous, a viscous lubricating fluid, to perform various functions, one of which being immunity. The mucosa, soft tissue which consists of the epithelium, lamina propria and muscularis mucosae, act as the our first line of defence against pathogens. This is aided by their production of mucin, a family of highly glycosilated proteins.

Mucin has been shown to effectively trap certain virions, namely HSV and HIV, reducing their rate of transmission.

## What should this page contain?

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* A clear and concise description of your project.
* A detailed explanation of why your team chose to work on this particular project.
* References and sources to document your research.
* Use illustrations and other visual resources to explain your project.

{% endblock %}

{% extends "layout.html" %}
{% block title %}Experiments{% endblock %}
{% block lead %}Describe the research, experiments, and protocols you used in your iGEM project.{% endblock %}
{% block page\_content %}

## What should this page contain?

---

Describe the research, experiments, and protocols you used in your iGEM project. These should be detailed enough for another team to repeat your experiments.

If you made Parts this year, please remember to put all information, characterization, and measurement data on the Part's Main Page on the [Registry](http://parts.igem.org/Main_Page).

## Inspirations

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* [2019 Nantes](https://2019.igem.org/Team%3ANantes/Experiments)
* [2019 TU Eindhoven](https://2019.igem.org/Team%3ATU_Eindhoven/Experiments)
* [2019 Mingdao](https://2019.igem.org/Team%3AMingdao/Demonstrate)
* [2020 Amsterdam](https://2020.igem.org/Team%3AAmsterdam/Experiments)
* [2020 NCTU Formosa](https://2020.igem.org/Team%3ANCTU_Formosa/Experiments)
* [2020 USAFA](https://2020.igem.org/Team%3AUSAFA/Experiments)

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{% extends "layout.html" %}
{% block title %}Results{% endblock %}
{% block lead %}You can describe the results of your project and your future plans here.{% endblock %}
{% block page\_content %}

## What should this page contain?

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* Clearly and objectively describe the results of your work.
* Future plans for the project.
* Considerations for replicating the experiments.

## Describe what your results mean

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* Interpretation of the results obtained during your project. Don't just show a plot/figure/graph/other, tell us what you think the data means. This is an important part of your project that the judges will look for.
* Show data, but remember **all measurement and characterization data must also be on the Part's Main Page on the [Registry](http://parts.igem.org/Main_Page).** Otherwise these data will not be in consideration for any medals or part awards!
* Consider including an analysis summary section to discuss what your results mean. Judges like to read what you think your data means, beyond all the data you have acquired during your project.

## Project Achievements

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You can also include a list of bullet points (and links) of the successes and failures you have had over your summer. It is a quick reference page for the judges to see what you achieved during your summer.

* A list of linked bullet points of the successful results during your project
* A list of linked bullet points of the unsuccessful results during your project. This is about being scientifically honest. If you worked on an area for a long time with no success, tell us so we know where you put your effort.

## Inspirations

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* [2019 Newcastle](https://2019.igem.org/Team%3ANewcastle/Results)
* [2019 Munich](https://2019.igem.org/Team%3AMunich/Results)
* [2019 Tec Chihuahua](https://2019.igem.org/Team%3ATec-Chihuahua/Results)
* [2020 Aalto Helsinki](https://2020.igem.org/Team%3AAalto-Helsinki/Results)
* [2020 GreatBay SCIE](https://2020.igem.org/Team%3AGreatBay_SCIE/Results)
* [2020 Queens Canada](https://2020.igem.org/Team%3AQueens_Canada/Results)

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