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Exploring Intronic RNA-Seq Read Counts for Machine Learning Phenotype Prediction

Zuiker, Thomas (author)

The inclusion of intronic reads in the downstream analysis of RNA-sequencing (RNA-seq) data has long been controversial. Recent studies show that intronic reads do contain relevant biological signal. Additionally, studies have discovered differential expression unique to intronic reads in certain diseases. Nevertheless, most disease prediction...

master thesis 2023

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Computational models for clinical drug response prediction: aligning transcriptomic data of patients and pre-clinical models

Mourragui, S.M.C. (author)

Extensive efforts in cancer research over the past decades have markedly improved diagnosis and treatments, leading to better outcomes for cancer patients. Paradoxically, however, these discoveries have begun to shed light on a level of complexity that rules out the emergence of a universal cancer treatment. As any tumor is now known to be...

doctoral thesis 2023

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Gene-Directed FtsZ Ring Assembly Generates Constricted Liposomes with Stable Membrane Necks

Godino, E. (author), Danelon, C.J.A. (author)

Mimicking bacterial cell division in well-defined cell-free systems has the potential to elucidate the minimal set of proteins required for cytoskeletal formation, membrane constriction, and final abscission. Membrane-anchored FtsZ polymers are often regarded as a sufficient system to realize this chain of events. By using purified FtsZ and...

journal article 2023

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Clonal Amplification-Enhanced Gene Expression in Synthetic Vesicles

Abil, Z. (author), Restrepo Sierra, A.M. (author), Danelon, C.J.A. (author)

In cell-free gene expression, low input DNA concentration severely limits the phenotypic output, which may impair in vitro protein evolution efforts. We address this challenge by developing CADGE, a strategy that is based on clonal isothermal amplification of a linear gene-encoding dsDNA template by the minimal Φ29 replication machinery and...

journal article 2023

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The interplay between metabolic stochasticity and cAMP-CRP regulation in single E. coli cells

Wehrens, Martijn (author), Krah, Laurens H.J. (author), Towbin, Benjamin D. (author), Hermsen, Rutger (author), Tans, S.J. (author)

The inherent stochasticity of metabolism raises a critical question for understanding homeostasis: are cellular processes regulated in response to internal fluctuations? Here, we show that, in E. coli cells under constant external conditions, catabolic enzyme expression continuously responds to metabolic fluctuations. The underlying...

journal article 2023

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Keeping still life away from death: Functions and dynamics of gene expression during dormacy of Saccharomyces cerevisiae spores

Maire, T.T.H. (author)

While life is present everywhere on earth, each individual species can only grow and proliferate in a specific set of conditions. Moreover due to inherent fluctuation of the environment, individual organisms are often periodically confronted to stressful conditions that prohibit growth, reproduction and increase mortality. One of the most common...

doctoral thesis 2022

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Expression of a gene-encoded FtsZ-based minimal machinery to drive synthetic cell division

Godino, E. (author)

The Christophe Danelon lab is involved in the long-term effort to construct an autonomous minimal cell using a bottom-up approach. Our goal is to achieve self-maintenance, selfreproduction, and evolution of a liposome compartment containing a minimal genome and a cell-free gene expression system. Self-reproduction requires splitting of the...

doctoral thesis 2022

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How does an organism extract relevant information from transcription factor concentrations?

Bauer, M.S. (author)

How does an organism regulate its genes? The involved regulation typically occurs in terms of a signal processing chain: an externally applied stimulus or a maternally supplied transcription factor leads to the expression of some downstream genes, which, in turn, are transcription factors for further genes. Especially during development, these...

review 2022

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Genetically encoded phospholipid production for autonomous synthetic cell proliferation

Blanken, D.M. (author)

Cells, the building blocks of life, are vastly complex. This complexity confers to every living organism the ability to maintain oneself, reproduce oneself, and evolve. Creating a minimal system from nonliving components that is capable of self-maintenance, self-reproduction, and evolvability, will greatly increase our understanding of life....

doctoral thesis 2021

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Shaping Liposomes by Cell-Free Expressed Bacterial Microtubules

Kattan, J.M. (author), Doerr, A. (author), Dogterom, A.M. (author), Danelon, C.J.A. (author)

Genetic control over a cytoskeletal network inside lipid vesicles offers a potential route to controlled shape changes and DNA segregation in synthetic cell biology. Bacterial microtubules (bMTs) are protein filaments found in bacteria of the genus Prosthecobacter. They are formed by the tubulins BtubA and BtubB, which polymerize in the...

journal article 2021

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Potential associations between immune signaling genes, deactivated microglia, and oligodendrocytes and cortical gray matter loss in patients with long-term remitted Cushing's disease

Bauduin, S.E.E.C. (author), den Rooijen, I.L.B. (author), Meijer, M. (author), van der Werff, S.J.A. (author), Keo, D.L. (author), Dzyubachyk, O. (author), Pereira, A.M. (author), Giltay, E.J. (author), van der Wee, N.J.A. (author), Meijer, O.C. (author), Mahfouz, A.M.E.T.A. (author)

Introduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent...

journal article 2021

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Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s Disease

Keo, D.L. (author), Dzyubachyk, Oleh (author), Van Der Grond, Jeroen (author), van Hilten, Jacobus J. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)

Cortical atrophy is a common manifestation in Parkinson’s disease (PD), particularly in advanced stages of the disease. To elucidate the molecular underpinnings of cortical thickness changes in PD, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and patterns of cortical thickness...

journal article 2021

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Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

Ragusi, Max A.A. (author), Bismeijer, Tycho (author), van der Velden, Bas H.M. (author), Loo, Claudette E. (author), Canisius, Sander (author), Wesseling, Jelle (author), Wessels, L.F.A. (author), Elias, Sjoerd G. (author), Gilhuijs, Kenneth G.A. (author)

Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included...

journal article 2021

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The Cancer SENESCopedia: A delineation of cancer cell senescence

Jochems, Fleur (author), Thijssen, Bram (author), De Conti, Giulia (author), Jansen, Robin (author), Pogacar, Ziva (author), Groot, Kelvin (author), Wang, Liqin (author), Schepers, Arnout (author), Wessels, L.F.A. (author)

Cellular senescence is characterized as a stable proliferation arrest that can be triggered by multiple stresses. Most knowledge about senescent cells is obtained from studies in primary cells. However, senescence features may be different in cancer cells, since the pathways that are involved in senescence induction are often deregulated in...

journal article 2021

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Biosynthesis of protein filaments for the creation of a minimal cell

Kattan, J.M. (author)

Humanity has achieved to decipher the most fundamental mechanics of cellular life. Nevertheless, despite intense efforts there are still considerable gaps in our understanding of cellular processes. Traditionally, biologists investigate life by observation of existing lifeforms. In order to assign functions to biological components, it is common...

doctoral thesis 2020

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Dormancy-to-death transition in yeast spores occurs due to gradual loss of gene-expressing ability

Maire, T.T.H. (author), Allertz, T. (author), Betjes, M.A. (author), Youk, H.O. (author)

Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains...

journal article 2020

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Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort

Niemantsverdriet, Ellis (author), van den Akker, E.B. (author), Boeters, Debbie M. (author), van den Eeden, Susan J.F. (author), Geluk, Annemieke (author), van der Helm-van Mil, Annette H.M. (author)

Background: Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop...

journal article 2020

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DNA sequence encodes the position of DNA supercoils

Kim, S.H. (author), Ganji, M. (author), Kim, E. (author), van der Torre, J. (author), Abbondanzieri, E. (author), Dekker, C. (author)

The three-dimensional organization of DNA is increasingly understood to play a decisive role in vital cellular processes. Many studies focus on the role of DNA-packaging proteins, crowding, and confinement in arranging chromatin, but structural information might also be directly encoded in bare DNA itself. Here, we visualize plectonemes ...

journal article 2018

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Natriuretic peptides in post-mortem brain tissue and cerebrospinal fluid of non-demented humans and Alzheimer's disease patients

Mahinrad, Simin (author), Bulk, Marjolein (author), Van Der Velpen, Isabelle (author), Mahfouz, A.M.E.T.A. (author), Van Roon-Mom, Willeke (author), Fedarko, Neal (author), Yasar, Sevil (author), Sabayan, Behnam (author), Van Heemst, Diana (author), Van Der Weerd, Louise (author)

Animal studies suggest the involvement of natriuretic peptides (NP) in several brain functions that are known to be disturbed during Alzheimer's disease (AD). However, it remains unclear whether such findings extend to humans. In this study, we aimed to: (1) map the gene expression and localization of NP and their receptors (NPR) in human...

journal article 2018

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Virus-inspired dna replication coupled with gene expression in a minimal cell framework

van Nies, P.Y.B. (author)

doctoral thesis 2017