Project description:Dinoflagellates are phytoplanktonic organisms found in both freshwater and marine habitats. They are often studied because related to harmful algal blooms responsible for impacts on ecosystem functioning, economic damages for aquaculture and fishery industries and/or deleterious impacts for human health. In addition they are also known to produce bioactive compounds, such as for the treatment of cancer or beneficial effects for the treatment of Alzheimer’s disease. The dinoflagellate Amphidinium sp. is a cosmopolitan dinoflagellate species known to produce both cytotoxic and beneficial compounds. However, several studies reported that environmental changes (e.g. nutrient starvation, UV radiation and ocean acidification) may alter this production. The aim of this study was to sequence the full transcriptome of the dinoflagellate Amphidinium carterae in both nitrogen- starved and -repleted culturing conditions (1) to evaluated its response to nitrogen starvation, (2) to look for possible polyketide synthases (PKSs), involved in the synthesis of various compounds, in this studied clone, (3) if present, to evaluate if nutrient starvation can influence PKS activity, (4) to test strain cytotoxicity on human cells and (5) to look for other possible enzymes/proteins of biotechnological interest.
Project description:Over the last 10 years, technological advances in molecular biology enabled a more accurate genomic characterization of tumors. For each tumor location, this led to the identification of subgroups with similar molecular characteristics. This identification allowed the development of targeted therapies and thus to improve the patient prognosis. This molecular characterization has also revealed the tumor heterogeneity. It may be the cause of treatment resistance and therefore of relapses. Additionally, tumor cells are in constant dialogue with their microenvironment composed of different immune or non immune cells. This microenvironment is now targeted in cancer treatment.
To date, there are few studies that combine a deep genomic characterization of both tumor and tumor microenvironment of the patient. Combining the two types of studies on the same tumor should help to define new therapeutic targets and should allow a combination of targeted and immunomodulatory therapies. To this end, our project is to conduct an exhaustive integrated exploratory analysis at genomic, transcriptomic and immunological levels of 3 tumor types (in colon, kidney and liver cancer).
Project description:Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study found that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetrically distribution along mature transcripts. In Amphidinium carterae, we identified 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many involved in regulating carbon and nitrogen metabolism. With enrichment within 3'UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion led to a significant decrease in mRNA m1A. Furthermore, our analysis revealed that distinctive patterns of m1A modification influence the expression of metabolism-related genes through translation control. Thus, this study provides a comprehensive map of m1A in dinoflagellate mRNA, highlighting its crucial role as a post-transcriptional regulatory layer and enhancing the understanding of mRNA m1A modification.
Project description:Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study found that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetrically distribution along mature transcripts. In Amphidinium carterae, we identified 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many involved in regulating carbon and nitrogen metabolism. With enrichment within 3'UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion led to a significant decrease in mRNA m1A. Furthermore, our analysis revealed that distinctive patterns of m1A modification influence the expression of metabolism-related genes through translation control. Thus, this study provides a comprehensive map of m1A in dinoflagellate mRNA, highlighting its crucial role as a post-transcriptional regulatory layer and enhancing the understanding of mRNA m1A modification.
Project description:Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study found that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetrically distribution along mature transcripts. In Amphidinium carterae, we identified 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many involved in regulating carbon and nitrogen metabolism. With enrichment within 3'UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion led to a significant decrease in mRNA m1A. Furthermore, our analysis revealed that distinctive patterns of m1A modification influence the expression of metabolism-related genes through translation control. Thus, this study provides a comprehensive map of m1A in dinoflagellate mRNA, highlighting its crucial role as a post-transcriptional regulatory layer and enhancing the understanding of mRNA m1A modification.