Theses

@phdthesis{nokey,

title = {Reston and Zaire ebolavirus life cycle and host cellular response},

author = {Nelly F. Mostajo},

doi = {10.22032/dbt.49230},

year  = {2021},

date = {2021-04-14},

urldate = {2021-04-14},

abstract = {Ebolaviruses are negative strand RNA viruses which are known to cause Ebola virus disease (EVD) with a fatal outcome in primates. All five species of Ebolavirus can infect humans, but only four lead to EVD. The Ebolavirus with the most provoked outbreaks and highest fatality rate (above 80%) is Zaire ebolavirus (EBOV), while the one without any provoke symptoms in humans is Reston ebolavirus (RESTV). In order to determine the features which lead to the different outcomes from EBOV and RESTV the cellular response against these viruses, and the divergence between RESTV and EBOV life cycle inside human cells was investigated. To study the cellular response RNA of two human cell lines (HuH7 and THP1) infected with RESTV, EBOV and uninfected (Mock) at two different time points was analyzed. Using whole transcriptome screening with smallRNAseq, Microarray, de novo annotation and expression profiles it was possible to elucidate that the cellular response against RESTV and EBOV infection differs the most at 3 h p.i., this was consistent in HuH7 and THP1 cell lines. The transcriptomic study showed RESTV and EBOV stimulate a distinct set of genes related to cellular entry. Also, the transcriptomic data suggests EBOV transcribes and replicates faster than RESTV, supported by cellular components like snoRNAs, while RESTV is similar to Mock in this aspect. This finding was backed with an entry assay which showed EBOV releases its content into the cytosol faster than RESTV, pointing to differences in entry pathway or a better time controlled response from the cell against RESTV. To understand the life cycle of RESTV and EBOV in human cells transcription/replication, inclusion bodies, nucleocapsid (NC) transport, viral particle formation, and infection was studied. Selected genes which were differentially expressed between RESTV and EBOV infected cells were further analyzed on the virus life cycle context.},

howpublished = {Friedrich-Schiller-Universität Jena},

keywords = {},

pubstate = {published},

tppubtype = {phdthesis}

}

2019

Srivastava, Akash

Whole-transcriptome changes in gene expression in multiple tissues across various organisms during aging PhD Thesis

2019.

Links | BibTeX

Barth, Emanuel

Insights into the regulation of aging PhD Thesis

2019.

Abstract | Links | BibTeX

@phdthesis{nokey,

title = {Insights into the regulation of aging},

author = {Emanuel Barth},

doi = {10.22032/dbt.40103},

year  = {2019},

date = {2019-08-09},

urldate = {2019-08-09},

abstract = {Aging is doubtlessly one of the most complex and multi-factorial biological processes we have encountered since the beginning of modern life sciences and the systematic study of human and animal biology. Despite many remarkable findings, aging remains an incompletely understood mechanism, causing several severe diseases, such as cardiovascular diseases, neurodegenerative diseases or cancer. It is associated with a progressive loss of cell functions that lead to a decline of tissue functions and finally resulting in death. Uncountable studies were performed over the last five decades to identify possible causes of how and why we age. Nevertheless, there is a still ongoing debate about the true molecular source of aging, giving rise to a variety of competing theories. Due to its highly complex nature, we have investigated aging from various perspectives, based on the gene expression of different species and tissues. We analyzed a huge set of RNA-Seq transcriptomic data to obtain new insights into the genetic regulation of aging and to identify conserved molecular processes that might be responsible for aging-related disorders. We found that each tissue shows its own distinct pattern of gene expressional changes with age, because they have to respond to different types of stress over time, leading to differing sources of molecular damage and subsequent stress responses. In particular, we could show this for four wellstudied aging-related processes: cellular senescence, inflammation, oxidative stress response and circadian rhythms. In addition, we could show that alternative splicing (i.e., the generation of multiple mRNA isoforms from single genes) is in general only slightly affected by aging and probably plays a secondary role in the overall aging process. In contrast, we found microRNAs (very small regulatory RNA molecules) to be important modulators of aging in all investigated pecies and tissues. Concluding, the results presented in this thesis describe aging as a stochastic process, leading to an accumulation of different kinds of molecular damage and the respective cellular stress responses. We have identified several genetic factors that could serve as potential diagnostic markers or even therapeutic targets, that could help in the future to slow down the progression of age-associated disorders or preventing them. Nevertheless, the subject of aging remains a challenging research field and many open questions still wait to be answered.},

howpublished = {Friedrich-Schiller-Universität Jena},

keywords = {},

pubstate = {published},

tppubtype = {phdthesis}

}

Aging is doubtlessly one of the most complex and multi-factorial biological processes we have encountered since the beginning of modern life sciences and the systematic study of human and animal biology. Despite many remarkable findings, aging remains an incompletely understood mechanism, causing several severe diseases, such as cardiovascular diseases, neurodegenerative diseases or cancer. It is associated with a progressive loss of cell functions that lead to a decline of tissue functions and finally resulting in death. Uncountable studies were performed over the last five decades to identify possible causes of how and why we age. Nevertheless, there is a still ongoing debate about the true molecular source of aging, giving rise to a variety of competing theories. Due to its highly complex nature, we have investigated aging from various perspectives, based on the gene expression of different species and tissues. We analyzed a huge set of RNA-Seq transcriptomic data to obtain new insights into the genetic regulation of aging and to identify conserved molecular processes that might be responsible for aging-related disorders. We found that each tissue shows its own distinct pattern of gene expressional changes with age, because they have to respond to different types of stress over time, leading to differing sources of molecular damage and subsequent stress responses. In particular, we could show this for four wellstudied aging-related processes: cellular senescence, inflammation, oxidative stress response and circadian rhythms. In addition, we could show that alternative splicing (i.e., the generation of multiple mRNA isoforms from single genes) is in general only slightly affected by aging and probably plays a secondary role in the overall aging process. In contrast, we found microRNAs (very small regulatory RNA molecules) to be important modulators of aging in all investigated pecies and tissues. Concluding, the results presented in this thesis describe aging as a stochastic process, leading to an accumulation of different kinds of molecular damage and the respective cellular stress responses. We have identified several genetic factors that could serve as potential diagnostic markers or even therapeutic targets, that could help in the future to slow down the progression of age-associated disorders or preventing them. Nevertheless, the subject of aging remains a challenging research field and many open questions still wait to be answered.

Riege, Konstantin

Annotation of non-coding RNAs and examination of Next Generation Sequencing data of pathogenic organisms PhD Thesis

2019.

Links | BibTeX