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Monitoring endogenous GPCRs: lessons for drug design

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196517 Year: Pages: 134 DOI: 10.3389/978-2-88919-651-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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G protein-coupled receptors (GPCRs) are integral membrane proteins forming the fourth largest superfamily in the human genome. Many of these receptors play key physiological roles and several pathologies have been associated with receptor functional abnormalities. GPCRs therefore represent important goals for drug design in pharmaceutical companies since they constitute the target of about one third of the drugs currently on the market. However, endogenous GPCRs are most often difficult to study because of a lack of tools to target them specifically and single out their response to physiological or drug-elicited stimulations. Hence, studies mostly focused on recombinant receptors expressed in a variety of cellular models that do not always closely reflect the receptor natural environment and often deal with levels of expression exceeding by far physiological ranges. Recent technological developments combining for example genetically modified animals and advanced imaging approaches have improved our ability to visualize endogenous GPCRs. To date, trailing receptor activation, subsequent intracellular redistribution, changes in signaling cascade up to integrated response to a drug-elicited stimulation is at hand though the impact of a physiological challenge on receptor dynamics remains a major issue. Data however suggest that the receptor may embrace a different fate depending on the type of stimulation in particular if sustained or repeated. This suggests that current drugs may only partially mimic the genuine response of the receptor and may explain, at least in part, their secondary effects. Commonalities and specificities between physiological and drug-induced activation can thus represent valuable guidelines for the design of future drugs.

Insights into Microbe-Microbe Interactions in Human Microbial Ecosystems: Strategies to be Competitive

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450527 Year: Pages: 116 DOI: 10.3389/978-2-88945-052-7 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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All parts of our body having communication with the external environment such as the skin, vagina, the respiratory tract or the gastrointestinal tract are colonized by a specific microbial community. The colon is by far the most densely populated organ in the human body. The pool of microbes inhabiting our body is known as “microbiota” and their collective genomes as “microbiome”. These microbial ecosystems regulate important functions of the host, and their functionality and the balance among the diverse microbial populations is essential for the maintenance of a “healthy status”. The impressive development in recent years of next generation sequencing (NGS) methods have made possible to determine the gut microbiome composition. This, together with the application of other high throughput omic techniques and the use of gnotobiotic animals has greatly improved our knowledge of the microbiota acting as a whole. In spite of this, most members of the human microbiota are largely unknown and remain still uncultured. The final functionality of the microbiota is depending not only on nutrient availability and environmental conditions, but also on the interrelationships that the microorganisms inhabiting the same ecological niche are able to establish with their partners, or with their potential competitors. Therefore, in such a competitive environment microorganisms have had to develop strategies allowing them to cope, adapt, or cooperate with their neighbors, which may imply notable changes at metabolic, physiological and genetic level. The main aim of this Research Topic was to contribute to better understanding complex interactions among microorganisms residing in human microbial habitats.All parts of our body having communication with the external environment such as the skin, vagina, the respiratory tract or the gastrointestinal tract are colonized by a specific microbial community. The colon is by far the most densely populated organ in the human body. The pool of microbes inhabiting our body is known as “microbiota” and their collective genomes as “microbiome”. These microbial ecosystems regulate important functions of the host, and their functionality and the balance among the diverse microbial populations is essential for the maintenance of a “healthy status”. The impressive development in recent years of next generation sequencing (NGS) methods have made possible to determine the gut microbiome composition. This, together with the application of other high throughput omic techniques and the use of gnotobiotic animals has greatly improved our knowledge of the microbiota acting as a whole. In spite of this, most members of the human microbiota are largely unknown and remain still uncultured. The final functionality of the microbiota is depending not only on nutrient availability and environmental conditions, but also on the interrelationships that the microorganisms inhabiting the same ecological niche are able to establish with their partners, or with their potential competitors. Therefore, in such a competitive environment microorganisms have had to develop strategies allowing them to cope, adapt, or cooperate with their neighbors, which may imply notable changes at metabolic, physiological and genetic level. The main aim of this Research Topic was to contribute to better understanding complex interactions among microorganisms residing in human microbial habitats.

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