Biological process | EPFL Graph Search

Biological processes are those processes that are vital for an organism to live, and that shape its capacities for interacting with its environment. Biological processes are made of many chemical reactions or other events that are involved in the persistence and transformation of life forms. Metabolism and homeostasis are examples. Biological processes within an organism can also work as bioindicators. Scientists are able to look at an individual's biological processes to monitor the effects of environmental changes. Regulation of biological processes occurs when any process is modulated in its frequency, rate or extent. Biological processes are regulated by many means; examples include the control of gene expression, protein modification or interaction with a protein or substrate molecule.

Homeostasis: regulation of the internal environment to maintain a constant state; for example, sweating to reduce temperature
Organization: being structurally composed of one or more cells&nbs

Identification of genetic interactors of ypa2 in Schizosaccharomyces pombe

Manuela Moraru

In this study, the fission yeast Schizosaccharomyces pombe was used as a model system to study the cellular signaling that underlies cell cycle progression. Phosphorylation plays an important part in the regulation of this process. Kinases catalyze the transfer of a phosphate group to a substrate, which may regulate its activity. Protein phosphatases oppose the activity of protein kinases; the balance of their activities regulates signaling flux in many signaling pathways. The Septation Initiation Network (SIN) is a signaling cascade that regulates cytokinesis in fission yeast. SIN signaling is triggered by a GTPase and is transduced by three protein kinases; phosphorylation plays an important role in controlling SIN signalling. Numerous genetic screens and biochemical analyses have identified phosphatases and kinases that regulate the SIN. The protein phosphatases Calcineurin/Protein Phosphatase 2B (PP2B) and Flp1p promote SIN signaling, while PP2A is a SIN inhibitor. PP2A is conserved and is activated by the chaperone Phosphatase Two A Phosphatase Activator (PTPA). S. pombe has two PTPA-related genes, ypa1 and ypa2; the deletion mutant of the latter rescues SIN mutants which cannot undergo cytokinesis, consistent with PP2A opposing SIN signaling. The phenotype of the deletion mutant of ypa2, indicates that it is involved in the control of cell polarity, cell growth, mitotic commitment and cytokinesis. In this study, we characterized the hypomorphic allele ypa2-S2 which rescues SIN mutants, but is otherwise largely normal. ypa2-s2 was used as bait in a synthetic genetic array screen, to identify genes whose products compensate for reduced function of Ypa2p. A large number of hits were identified, of which approximately ninety percent are novel genetic interactors of ypa2. Validation studies indicated that eighty percent of the interactions seen in the high-throughput screen can be reconstructed. The identified genes regulate several biological processes, including signal transduction and protein phosphorylation. This prompted us to further characterize the roles of Ckb1p and Flp1p, in regulating cytokinesis signaling. Ckb1p is a regulatory subunit for Casein Kinase II (CK II), which was previously implicated in polar growth. The phenotype of the mutant ypa2-S2 ckb1-â indicates that Ckb1p, similar to Ypa2p, contributes to the regulation of mitotic commitment and cytokinesis signaling. Furthermore, ckb1-â showed negative genetic interaction with PP2A and SIN mutants. Flp1p is a protein phosphatase that was reported to regulate mitotic commitment and to promote SIN signaling. The double mutant between ypa2-S2 and flp1-â showed cell separation defects and phenotypic analysis of double mutants between flp1-â and PP2A mutants indicates that these phosphatases cooperate in cell separation. Overall, this work has uncovered novel facets of the regulation of cytokinesis in S. pombe, implicating CK II in controlling SIN signaling, and uncovering cooperative interactions between different phosphatases in controlling cytokinesis.

EPFL2016

A new non-toxic chemically cross-linked ELP hydrogel for in situ protein delivery

Karine Ciapala

Proteins play an essential role in all biological processes and have been attracting more and more attention as drug candidates due to their high specificity and activity. However, their use as therapeutics has been seriously held back given that their ability to be effectively and conveniently delivered is problematic. Indeed, simple oral administration is ineffective since proteins are degraded in the digestive tract. Until now, these therapeutic agents were delivered by infusions or frequent injections. But this causes serious problems, as the compound does not get delivered in a prolonged continuous manner. Additionally, injections are also problematic as patients are reluctant to use needles unless there illness is life threatening. That is why focus has grown over the last years on developing novel delivery systems for proteins. Amongst the various types of delivery systems that exist, hydrogel based ones are very promising, as they possess remarkable biomimetic properties. The hydrogels that are chemically cross-linked are stronger than their counterparts, the physical hydrogels. An appealing approach to protein delivery that is more and more sought is to form the hydrogel in situ from an injected aqueous polymer solution and to use the formed gel as a depot for the sustained release of the protein. Oxygen sensitive gellation is an interesting stimulus to form these gels, but has not been successfully developed, as the gelling kinetics are too slow. Therefore, research groups have turned to the use of toxic chemicals to speed up the reaction. Elastin-like poylpeptides (ELP) are artificial biopolymers that are composed of a pentapeptide repeat. This repeat consists of Val-Pro-Gly-Xaa-Gly, where Xaa denotes a guest residue. An interesting characteristic of ELPs is that they are thermally responsive. Meaning, that when in solution they go through a lower critical solution temperature (LCST) transition. Below their LCST they are soluble in water and above their LCST they are insoluble. ELPs are well suited for drug delivery applications for many reasons such as their biocompatibility. The ELP that is studied is ELP9 Gel. Its guest residues are Val, Ala and Cys in a ratio of 1:14:1 respectively. As this ELP has cysteines it has the capacity to form a gel via cross-linking of the thiols groups by oxidation. The rheological tests that were carried out showed that this ELP9 Gel has all the characteristics of a gel. Furthermore, its gelling kinetics were greatly increased by heating it, but still remain too long for in situ applications. This suggests that the LCST behaviour of ELPs seems to play some role in favouring the cross-linking. But further controls remain to be done to confirm this hypothesized tandem process. A delivery strategy that involved this ELP9 Gel and Blue Fluorescent Proteins (BFP) with added cysteines was not successful as the molecular biology to obtain the modified proteins failed. However, the elaboration of a fusion peptide between Glucagon-Like-Peptide-1 (GLP-1) and ELP9 Gel was accomplished. The preliminary activity assay showed a reduced activity in comparison to the GLP-1 peptide alone. Unfortunately this ELP9 Gel has a setback due to its slow gelling time. Therefore, before continuing the research on the delivery strategies, it would be wiser to create a better ELP. If a new ELP with a higher cysteine concentration and lower transition temperature can be created, its gelling kinetics may be favourable for in situ protein delivery applications and thus, a chemically cross-linked hydrogel that does not require any toxic cross-linker would be available. This would be a big step in creating a very robust hydrogel for protein delivery applications but also for tissue regeneration

2009

Sirtuin 2 Deficiency Increases Bacterial Phagocytosis by Macrophages and Protects from Chronic Staphylococcal Infection

Johan Auwerx, Tytti Heinonen, Marc Pfefferlé

Sirtuin 2 (SIRT2) is one of the seven members of the family of NAD(+)-dependent histone deacetylases. Sirtuins target histones and non-histone proteins according to their subcellular localization, influencing various biological processes. SIRT2 resides mainly in the cytoplasm and regulates cytoskeleton dynamics, cell cycle, and metabolic pathways. As such, SIRT2 has been implicated in the pathogenesis of neurodegenerative, metabolic, oncologic, and chronic inflammatory disorders. This motivated the development of SIRT2-directed therapies for clinical purposes. However, the impact of SIRT2 on antimicrobial host defense is largely unknown. Here, we address this question using SIRT2 knockout mice. We show that SIRT2 is the most highly expressed sirtuin in myeloid cells, especially macrophages. SIRT2 deficiency does not affect immune cell development and marginally impacts on intracellular signaling and cytokine production by splenocytes and macrophages. However, SIRT2 deficiency enhances bacterial phagocytosis by macrophages. In line with these observations, in preclinical models, SIRT2 deficiency increases survival of mice with chronic staphylococcal infection, while having no effect on the course of toxic shock syndrome toxin-1, LPS or TNF-induced shock, fulminant Escherichia coli peritonitis, sub-lethal Klebsiella pneumoniae pneumonia, and chronic candidiasis. Altogether, these data support the safety profile of SIRT2 inhibitors under clinical development in terms of susceptibility to infections.

Frontiers Media Sa2017