Periodic Reporting for period 1 - IMMUNO_CRC (Microbiota-immune interaction in colorectal cancer)
Berichtszeitraum: 2017-04-01 bis 2019-03-31
Colorectal cancer (CRC) is one of the most common cancers in humans, with nearly 1.4 million new cases diagnosed globally in 2012. In Ireland, CRC is the third leading cause of death in women and the second cancer-mortality in men (National Cancer Registry 2019). Given the high morbidity and mortality from this disease, it is vital to develop new strategies and ways of thinking to improve the patients’ outcomes. Significant risk factors for CRC include diets rich in fat and red meat, obesity, and chronic inflammation of the gastrointestinal tract, all of which are closely associated with changes in the gut microbiota. The gut microbiota is the community of trillions of microbes living in the intestine, which play an essential role in our health. An altered gut microbiota has been associated with CRC and previous studies have established an important role for some gut microbiota members in cancer progression, outcome and response to therapy. Therefore, strategies aimed at manipulating the tumour-associated gut microbiota in CRC represent a promising therapeutic approach for patients.
The overall goal of the IMMUNO-CRC project was to understand how certain gut microbiota groups, identified in CRC patients may alter the immune response and influence clinical outcome. To achieve this goal, we used a combination of advanced techniques, including microbiome sequencing, gene transcriptomics, histology and multi-colour flow cytometry. Also, we transferred human-associated microbial populations from patients with CRC into a well-established mouse model of human CRC, ensuring, therefore, a direct translational potential for human medicine. A parallel goal of the IMMUNO-CRC project was to foster the career development of the researcher.
The overall goal of the IMMUNO-CRC project was to understand how certain gut microbiota groups, identified in CRC patients may alter the immune response and influence clinical outcome. To achieve this goal, we used a combination of advanced techniques, including microbiome sequencing, gene transcriptomics, histology and multi-colour flow cytometry. Also, we transferred human-associated microbial populations from patients with CRC into a well-established mouse model of human CRC, ensuring, therefore, a direct translational potential for human medicine. A parallel goal of the IMMUNO-CRC project was to foster the career development of the researcher.
The IMMUNO-CRC project was conducted via 6 work packages (WP). Using a variety of molecular and sequencing techniques in WP1-3, we have:
1. Established a preclinical mouse model of CRC (i.e. a mouse that shows the biological characteristics of human colorectal cancer disease), using microbiota from patients with CRC.
2. Used this mouse model to study how different microbiota groups affect the immune response, and in turn how this controls the progression of CRC.
3. Shown that a ‘protective’ microbiota-type reduced tumour growth
4. Shown that different microbiota types affect cancer development at different rates
The IMMUNO-CRC project contributed to enhancing the knowledge and expertise of the fellow in the most current techniques and approaches in microbial genomics, metagenomics and microbiota-host interactions. The project has also brought together researchers from very diverse backgrounds within the host lab in a collaborative manner.
In WP 4, for technical training and transfer of knowledge, the fellow attended 6 intensive training workshops and courses, including the prestigious Scientists Teaching Science online course, organized by the New York Academy of Sciences. She attended 1 international conference and she will be giving a short talk at the Microbiome Meeting (virtual), organized by Cold Spring Harbor Laboratory, in October. To transfer knowledge, she provided supervision and mentoring of early career researchers.
In WP5, for personal and career development, the fellow acquired transferrable skills in communication and leadership, as she co-founded and chairs the APC Postdoc Association. One of her roles as the chair of the APC Postdoc Association is to organize career seminars for postdocs, including interviewing leaders in the microbiome field. Last spring 2020 semester, the fellow also started lecturing the Immunology Course to undergraduate students at University College Cork. This involved the preparation of lectures, support material for the class, lectures and exam preparation. The fellow also attended the EMBO Laboratory Leadership Course for Postdocs. Finally, in June 2017, the fellow was awarded a PARSUK Xperience Supervisor Award, funded by PARSUK and Fundação Calouste Gulbenkian.
In WP 6, for communication and dissemination of results, there are currently 3 original research articles in preparation, which are expected to be submitted by the end of the year. As the Coordinator and Project Manager of the Native Scientist workshops in Ireland, the fellow has been heavily involved in education and science communication to younger pupils with an ethnic minority or migrant background.
1. Established a preclinical mouse model of CRC (i.e. a mouse that shows the biological characteristics of human colorectal cancer disease), using microbiota from patients with CRC.
2. Used this mouse model to study how different microbiota groups affect the immune response, and in turn how this controls the progression of CRC.
3. Shown that a ‘protective’ microbiota-type reduced tumour growth
4. Shown that different microbiota types affect cancer development at different rates
The IMMUNO-CRC project contributed to enhancing the knowledge and expertise of the fellow in the most current techniques and approaches in microbial genomics, metagenomics and microbiota-host interactions. The project has also brought together researchers from very diverse backgrounds within the host lab in a collaborative manner.
In WP 4, for technical training and transfer of knowledge, the fellow attended 6 intensive training workshops and courses, including the prestigious Scientists Teaching Science online course, organized by the New York Academy of Sciences. She attended 1 international conference and she will be giving a short talk at the Microbiome Meeting (virtual), organized by Cold Spring Harbor Laboratory, in October. To transfer knowledge, she provided supervision and mentoring of early career researchers.
In WP5, for personal and career development, the fellow acquired transferrable skills in communication and leadership, as she co-founded and chairs the APC Postdoc Association. One of her roles as the chair of the APC Postdoc Association is to organize career seminars for postdocs, including interviewing leaders in the microbiome field. Last spring 2020 semester, the fellow also started lecturing the Immunology Course to undergraduate students at University College Cork. This involved the preparation of lectures, support material for the class, lectures and exam preparation. The fellow also attended the EMBO Laboratory Leadership Course for Postdocs. Finally, in June 2017, the fellow was awarded a PARSUK Xperience Supervisor Award, funded by PARSUK and Fundação Calouste Gulbenkian.
In WP 6, for communication and dissemination of results, there are currently 3 original research articles in preparation, which are expected to be submitted by the end of the year. As the Coordinator and Project Manager of the Native Scientist workshops in Ireland, the fellow has been heavily involved in education and science communication to younger pupils with an ethnic minority or migrant background.
The results from the IMMUNO-CRC project has increased our understanding of how the microbiota-immune host interaction influences the development of CRC, which will be key for designing future prevention and treatment strategies targeting the microbiota. It will establish the foundation for the development of novel immunotherapeutics, and population risk-reduction strategies. This cross-cutting research directly relates the objective of Horizon 2020 Work Programme - Societal Challenge 1: Health, Demographic Change and Wellbeing, which aims to improve health and well-being outcomes to promote healthy and active learning.