The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

/pdf/initial-sequencing-and-analysis-of-the-human-genome-5dapk1rsx1.pdf

Initial sequencing and analysis of the human genome.

Salt and drought stress signal transduction consists of ionic and osmotic homeostasis signaling pathways, detoxification (i.e., damage control and repair) response pathways, and pathways for growth regulation. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. Osmotic stress activates several protein kinases including mitogen-activated kinases, which may mediate osmotic homeostasis and/or detoxification responses. A number of phospholipid systems are activated by osmotic stress, generating a diverse array of messenger molecules, some of which may function upstream of the osmotic stress-activated protein kinases. Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes.

/pdf/salt-and-drought-stress-signal-transduction-in-plants-4bj87ki2ww.pdf

Salt and drought stress signal transduction in plants

We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.

/pdf/genomic-expression-programs-in-the-response-of-yeast-cells-4xrnicxf7t.pdf

Genomic expression programs in the response of yeast cells to environmental changes.

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...

Plant cellular and molecular responses to high salinity.

We compared the nucleotide sequences of 3 yeast invertase genes in regions where the homology is better than 90% In the noncoding region 40 gaps of 1–61 bases were found This is about half as much as the nucleotide substitutions in the same sequences We grouped the gaps into 5 categories by their length and the characteristics of their sequences Group I gaps are about 20 nucleotides long and are flanked by repeated sequence of 6 bases which may trigger the deletion of one of the repeats and the sequence between the repeats Group II gaps are characterized by a small repeated sequence which is missing in one of the invertase genes Gaps which occur in sequences exclusively made up of one of the 4 bases are summarized in group III The 4 gaps in group IV do not show any of these sequence characteristics and they are all just one base long A 61 nucleotide sequence found in only one of the invertase genes seems to be of complex origin We conclude that small repeated sequences or monotonous sequences are prone to deletion or insertion mutations

Comparison of the nucleotide sequences of a yeast gene family. II. Analysis of spontaneous deletions and insertions.

Osmoregulation, i.e. the active control of the cellular water balance, encompasses homeostatic mechanisms crucial for life. The osmoregulatory system in the yeast Saccharomyces cerevisiae is particularly well understood, although many details of the regulatory mechanisms still remain to be discovered. Central to yeast osmoregulation is the high osmolarity glycerol (HOG) signalling network, a branched mitogen-activated protein kinase (MAPK) pathway that converges on the MAPK Hog1. Active Hog1 controls numerous cellular processes in the cytosol (cell cycle, translation, ion, water and glycerol transport and central metabolism) as well as the expression of numerous genes. In order to achieve a quantitative understanding and to fit different processes in a temporal order, we have generated a comprehensive mathematical model of yeast osmoregulation in collaboration with theoreticians. Using model simulation and quantitative time-course experimentation, we have analysed mechanisms of feedback control of the HOG pathway. These studies illustrate how a signalling pathway combines rigorous feedback control with maintenance of signalling competence, as required for a system controlling cell homeostasis.

Chapter 8 Integrative analysis of yeast osmoregulation

Major Intrinsic Proteins (MIPs) form a large family of integral membrane channel proteins involved in the transport of water and small uncharged solutes such as glycerol and urea. Forming the largest subgroup in the MIP family, aquaporins (AQPs) are water-selective channels facilitating rapid water flow across cellular membranes. Because water movement in cells and tissues is central to life, it is not surprising that AQPs have been identified in mammals, plants, invertebrates, amphibia, prokaryotes and recently in the baker’s yeast, Saccharomyces cerevisiae. The yeast genome contains 2 open reading frames (ORFs) that are homologous to plant aquaporin genes (Andre 1995), and 75.7% identical to each other. Those were recently renamed AQY1 (ORF YPR192w) and AQY2 (overlapping ORFs YLL052c–053c).

Aquaporin Water Channels in Saccharomyces Cerevisiae

Membrane proteins play key roles at the interface between the cell and its environment by mediating selective import and export of molecules via plasma membrane channels. Despite a multitude of studies on transmembrane channels, understanding of their dynamics directly within living systems is limited. To address this, we correlated molecular scale information from living cells with real time changes to their microenvironment. We employed super-resolved millisecond fluorescence microscopy with a single-molecule sensitivity, to track labelled molecules of interest in real time. We use as example the aquaglyceroporin Fps1 in the yeast Saccharomyces cerevisiae to dissect and correlate its stoichiometry and molecular turnover kinetics with various extracellular conditions. In this way we shed new light on aspects of architecture and dynamics of glycerol-permeable plasma membrane channels.

https://www.biorxiv.org/content/biorxiv/early/2020/02/27/2020.02.27.967638.full.pdf

Correlating single-molecule characteristics of the yeast aquaglyceroporin Fps1 with environmental perturbations directly in living cells

Microfluidic systems in combination with microscopy (e.g., fluorescence) can be a powerful tool to study, at single-cell level, the behavior and morphology of biological cells after uptake of glucose. Here, we briefly discuss the advantages of using microfluidic systems. We further describe how microfluidic systems are fabricated and how they are utilized. Finally, we discuss how the large amount of data can be analyzed in a “semi-automatic” manner using custom-made software. In summary, we provide a guide to how to use microfluidic systems in single-cell studies.

Stefan Hohmann

Papers

Comparison of the nucleotide sequences of a yeast gene family. II. Analysis of spontaneous deletions and insertions.

Chapter 8 Integrative analysis of yeast osmoregulation

Aquaporin Water Channels in Saccharomyces Cerevisiae

Correlating single-molecule characteristics of the yeast aquaglyceroporin Fps1 with environmental perturbations directly in living cells

Applying Microfluidic Systems to Study Effects of Glucose at Single-Cell Level