| dc.description.abstracteng | With the advent of high-throughput sequencing technologies, multi omics studies (genomics, transcriptomics, proteomics, and metabolomics) are becoming increasingly popular to decipher the molecular patterns in association with a disease/biological process. Access to such data has revolutionized the field of agriculture and it provides novel perspectives for several systems biology studies. Furthermore, the usage of multi-omics data has proven to be powerful and accurate to study the biological processes in association with the growth, development, adaptation and disease progression in an organism. Moreover, systems biology approaches enabled the integration of multi omics data to create a holistic understanding of the molecular mechanisms underpinning complex traits. In this thesis, I present the application projects which investigate the molecular mechanisms underlying the complex traits involved in (i) African Animal Trypanosomiasis disease progression in cattle breeds and (ii) the seed oil content of the oil crop Brassica napus.
Regarding my first project, African Animal Trypanosomiasis (AAT) is a disease caused by pathogenic trypanosomes which affects millions of livestock every year causing huge economic losses in agricultural production especially in sub-Saharan Africa. The disease is spread by the tsetse fly which carries the parasite in its saliva. During the disease progression, the cattle are prominently subjected to anaemia, weight loss, intermittent fever, chills, neuronal degeneration, and congestive heart failure. According to their different genetic programs governing the level of tolerance to AAT, cattle breeds are classified as either tolerant or susceptible. I focussed on the cattle breeds N’Dama and Boran which are known to be tolerant and susceptible to trypanosomiasis, respectively. Despite the rich literature on both breeds, the gene regulatory mechanisms of the underlying biological processes for their resistance and susceptibility have not been extensively studied. To address the limited knowledge, I analyzed a continuous transcription profiling time-series microarray dataset obtained from three tissues (liver-, spleen-, and lymph node tissues) of the two cattle breeds Boran and N’Dama, after being infected with Trypanosoma congolense. I attempted to capture the transcriptional events while considering the multistage progression process of AAT disease through the identification of monotonically expressed genes (MEGs). As a result, I identified several tissue-specific transcription factor (TF) cooperations for the tissues of both cattle breeds and explained the role of preferential partner choices of TFs in association with the trypanosusceptibility and trypanotolerance mechanisms. Furthermore, I focussed on the upstream regulatory processes underlying the multi-stage progression process of the AAT disease by identifying the unique, cattle breed-specific master regulators and over-represented signalling pathways for these two cattle breeds, respectively. Moreover, I deciphered the influence of downstream regulatory events involving the effector molecules and their complex interplay with the regulatory SNPs and gene expression.
In order to test the applicability of the bioinformatics pipeline from the first project on other species, I investigated the transcriptional regulation involved in governing the seed oil content in Brassica napus L. Knowledge regarding transcriptional regulation is crucial to gain insights into the developmental switches between the cultivars of Brassica napus, namely Zhongshuang11 (ZS11), a double-low accession with high-oil- content, and Zhongyou821 (ZY821), a double-high accession with low-oil-content. In my second project, I analyzed a time series RNA-seq data set of seed tissue from both cultivars by mainly focusing on the MEGs. The consideration of the MEGs enables the capturing of a multi-stage progression process that is orchestrated by the cooperative TFs and, thus, facilitates the understanding of the molecular mechanisms determining seed oil content. In this study, I reported that TF families, such as NAC, MYB, DOF, GATA, and HD-ZIP, are highly involved in the seed developmental process. Particularly, their preferential partner choices as well as changes in their gene expression profiles seem to be strongly associated with the differentiation of the oil content between the two cultivars.
In summary, my application project in animal sciences provides insights into genetic programs governing the susceptibility and tolerance mechanisms in cattle breeds Boran and N’Dama and therefore provides novel targets for therapeutic implications and future breeding programs. My second application project resulted in several potential targets for breeding purposes with respect to seed oil content in two cultivars of Brassica napus. | de |