Periodic Reporting for period 1 - SKINDEV (SKIN MICROBIAL DEVICES)
Berichtszeitraum: 2023-02-01 bis 2024-01-31
The utilization of genetic engineering technology applied to Cutibacterium acnes (C. acnes), a common inhabitant of the skin microbiome, represents a significant advancement in the field. By engineering C. acnes to produce specific therapeutics against AD and integrating innovative sensor technologies, the SSMDs have the capability to detect relevant skin signals and deliver therapeutic treatments in real-time.
The objectives outlined by SKINDEV - identifying key biomarkers for skin diseases, developing genetic tools for live detection of these biomarkers, implementing bacterial-produced therapeutics, and validating and improving the technology using Human Skin 3D models - demonstrate a comprehensive and systematic approach towards achieving their goal.
Overall, the vision of SKINDEV to revolutionize skin health management through personalized, effective, and convenient solutions reflects a significant step forward in the field of dermatological care and preventive medicine.
The objectives outlined by SKINDEV - identifying key biomarkers for skin diseases, developing genetic tools for live detection of these biomarkers, implementing bacterial-produced therapeutics, and validating and improving the technology using Human Skin 3D models - demonstrate a comprehensive and systematic approach towards achieving their goal.
Overall, the vision of SKINDEV to revolutionize skin health management through personalized, effective, and convenient solutions reflects a significant step forward in the field of dermatological care and preventive medicine.
Chronic skin inflammation, including conditions like atopic dermatitis (AD or atopic eczema) and psoriasis, affect at least 250 million patients worldwide. AD is highly common in Western countries with rising incidence rates and compromising a large pediatric patient population. Current therapies mostly target the immune system using monoclonal antibodies (e.g. Dupilumab) or small molecule drugs based on one-size-fits-all healthcare guidelines. These drugs are effective but compromise the immune system, posing significant side effects such as secondary opportunistic infection REF. These therapies are also expensive and, with the growing AD patient population, will pose a great economic burden on healthcare systems.
Our skin is inhabited by trillions of microbes commonly referred to as the microbiome. These bacteria are naturally adapted to live in our body as well as sense and respond to host biomarkers or environmental cues. Genetic engineering methodologies can transform these natural skin microbes and equip them to become smart devices, able to monitor health and diseases responding accordingly to treat a wide range of skin diseases. While engineered microbes already show encouraging results to treat metabolic disorders, infections or cancer in the gut, the examples of engineered bacteria on the skin are scarce.
The long-term vision of the SKINDEV consortium is to complement the human skin microbiome with Smart Skin Microbial Devices (SSMDs) in AD patients and other dermatological conditions as a new transformative healthcare system for treatment and monitoring of disease. We aim to make SSMDs applicable through innovative technologies like sensing applications in wearables to reach at-home on-demand skin health information and intervention. To reach this main goal we are focusing on:
Steppingstone 1: developing computational models of AD and the skin microbiome to guide how to engineer SSMD
Steppingstone 2: Genetic engineering to create sensing and actuation circuits in C. acnes
Steppingstone 3: Tissue engineering to create a high throughput skin organoid platform for AD.
We are developing these three key technologies for establishing a design-build-test cycle that enables us to develop SSMDs with sensing and actuation capabilities.
In conclusion, our SKINDEV project aims to generate a new paradigm for dermatological treatment using the natural adaptability of skin bacteria complemented with genetic engineering technologies. Our goal is to create skin devices or SSDMs to satisfy the current needs for AD and skin conditions management.
Our skin is inhabited by trillions of microbes commonly referred to as the microbiome. These bacteria are naturally adapted to live in our body as well as sense and respond to host biomarkers or environmental cues. Genetic engineering methodologies can transform these natural skin microbes and equip them to become smart devices, able to monitor health and diseases responding accordingly to treat a wide range of skin diseases. While engineered microbes already show encouraging results to treat metabolic disorders, infections or cancer in the gut, the examples of engineered bacteria on the skin are scarce.
The long-term vision of the SKINDEV consortium is to complement the human skin microbiome with Smart Skin Microbial Devices (SSMDs) in AD patients and other dermatological conditions as a new transformative healthcare system for treatment and monitoring of disease. We aim to make SSMDs applicable through innovative technologies like sensing applications in wearables to reach at-home on-demand skin health information and intervention. To reach this main goal we are focusing on:
Steppingstone 1: developing computational models of AD and the skin microbiome to guide how to engineer SSMD
Steppingstone 2: Genetic engineering to create sensing and actuation circuits in C. acnes
Steppingstone 3: Tissue engineering to create a high throughput skin organoid platform for AD.
We are developing these three key technologies for establishing a design-build-test cycle that enables us to develop SSMDs with sensing and actuation capabilities.
In conclusion, our SKINDEV project aims to generate a new paradigm for dermatological treatment using the natural adaptability of skin bacteria complemented with genetic engineering technologies. Our goal is to create skin devices or SSDMs to satisfy the current needs for AD and skin conditions management.
The achievements and ongoing work described here represent significant progress towards the goals of the SKINDEV project, particularly in the development and application of genetic tools and microbial strains for understanding host-microbe interactions and potential therapeutic interventions in atopic dermatitis (AD) and related skin conditions:
- Identification of Key Chemokines: This will enable researchers and clinicians to utilize this information for diagnostic and monitoring purposes.
- In Silico Modeling of Cell Resource Competition: Its validation in the lab, particularly by measuring production from Smart Skin Microbial Devices (SSMDs) constructed with different circuits, will further elucidate their efficacy and facilitate dissemination to the synthetic biology and metabolic engineering communities.
- Dynamic Interplay Between Skin and Microbial Species: This finding underscores the significance of developing SSMDs to aid in skin recovery and reinforces the objective of the grant to develop innovative approaches for AD treatment.
- Genetic Toolkit for C. acnes: The development of a genetic toolkit and optimized vector for C. acnes has the potential to significantly advance research on host-microbe interactions in the skin. Dissemination of these genetic parts among the scientific community will be essential for maximizing their impact and fostering collaboration in skin microbiome research.
- Developing an enhanced bacterial strain: The creation of an actuator strain with potential therapeutic activity in AD patients, represents significant strides towards the development of Smart Skin Microbial Devices (SSMDs).
- Bacterial interactions: The collaboration between RAD and ICa has yielded significant progress in understanding the interaction between the Smart Skin Microbial Device (SSMD) strain C. acnes and the AD-associated pathogen S. aureus. Utilizing the stratum corneum model, researchers can now investigate microbe-microbe interactions in co-culture, replicating the natural habitat of the skin microbiome.
- 3D skin models: The development of advanced organotypic models for different atopic dermatitis phenotypes has enhanced our understanding of disease endotypes and pathophysiology. This approach holds promise for accelerating the development of targeted therapies for specific AD subtypes.
- Bacterial engraftment methodology: The creation of a methodology to engraft live bacteria on tissue culture models, validated by the use of topical antibiotics, has garnered attention from both the scientific community and the lay press. This model provides a platform for investigating host-microbe interactions in healthy and diseased skin, with ongoing efforts to explore novel sequencing technologies like ciRNAseq for sensitive gene expression analysis.
Overall, these research endeavors contribute to advancing our understanding of AD pathophysiology and inform the development of novel diagnostic tools, therapeutic strategies, and SSMDs aimed at improving patient outcomes and addressing the unmet needs of individuals with AD
In regard to dissemination and communication results, the plan implemented by the SKINDEV project ensures consistency and visibility across all published articles. Guidelines, including publication standards, are established to maintain uniformity and quality in disseminating research findings to the scientific community and the general public.
To further amplify the project's visibility, UPF has taken the lead in content creation by developing a promotional video for SKINDEV. It aims to effectively communicate the significance of SKINDEV to a wider audience, fostering understanding and support for the project's goals and outcomes.
- Identification of Key Chemokines: This will enable researchers and clinicians to utilize this information for diagnostic and monitoring purposes.
- In Silico Modeling of Cell Resource Competition: Its validation in the lab, particularly by measuring production from Smart Skin Microbial Devices (SSMDs) constructed with different circuits, will further elucidate their efficacy and facilitate dissemination to the synthetic biology and metabolic engineering communities.
- Dynamic Interplay Between Skin and Microbial Species: This finding underscores the significance of developing SSMDs to aid in skin recovery and reinforces the objective of the grant to develop innovative approaches for AD treatment.
- Genetic Toolkit for C. acnes: The development of a genetic toolkit and optimized vector for C. acnes has the potential to significantly advance research on host-microbe interactions in the skin. Dissemination of these genetic parts among the scientific community will be essential for maximizing their impact and fostering collaboration in skin microbiome research.
- Developing an enhanced bacterial strain: The creation of an actuator strain with potential therapeutic activity in AD patients, represents significant strides towards the development of Smart Skin Microbial Devices (SSMDs).
- Bacterial interactions: The collaboration between RAD and ICa has yielded significant progress in understanding the interaction between the Smart Skin Microbial Device (SSMD) strain C. acnes and the AD-associated pathogen S. aureus. Utilizing the stratum corneum model, researchers can now investigate microbe-microbe interactions in co-culture, replicating the natural habitat of the skin microbiome.
- 3D skin models: The development of advanced organotypic models for different atopic dermatitis phenotypes has enhanced our understanding of disease endotypes and pathophysiology. This approach holds promise for accelerating the development of targeted therapies for specific AD subtypes.
- Bacterial engraftment methodology: The creation of a methodology to engraft live bacteria on tissue culture models, validated by the use of topical antibiotics, has garnered attention from both the scientific community and the lay press. This model provides a platform for investigating host-microbe interactions in healthy and diseased skin, with ongoing efforts to explore novel sequencing technologies like ciRNAseq for sensitive gene expression analysis.
Overall, these research endeavors contribute to advancing our understanding of AD pathophysiology and inform the development of novel diagnostic tools, therapeutic strategies, and SSMDs aimed at improving patient outcomes and addressing the unmet needs of individuals with AD
In regard to dissemination and communication results, the plan implemented by the SKINDEV project ensures consistency and visibility across all published articles. Guidelines, including publication standards, are established to maintain uniformity and quality in disseminating research findings to the scientific community and the general public.
To further amplify the project's visibility, UPF has taken the lead in content creation by developing a promotional video for SKINDEV. It aims to effectively communicate the significance of SKINDEV to a wider audience, fostering understanding and support for the project's goals and outcomes.