15th International Conference on Metabolomics & Systems Biology August 29-30, 2019 Vienna, Austria

Biography:

Abstract:

The vast majority of patients with end-stage renal disease are treated with intermittent hemodialysis as a form of renal replacement therapy. To investigate the impact of hemodialysis membrane material on vital protein removal, dialysates from 26 well-characterized hemodialysis patients were collected 5 min after beginning, during 5 h of treatment, as well as 5 min before ending of the dialysis sessions. Dialysis sessions were performed using either modified cellulose (n=12) (low-flux and high flux) or synthetic Polyflux (n=14) (low-flux and high-flux) dialyzer. Protein removal during hemodialysis was quantified and the dialysate proteome patterns were analyzed by 2-DE-MS and Western blot. There was a clear correlation between the type of membrane material and the amount of protein removed. Synthetic Poly flux membranes exhibit strong interaction with plasma proteins resulting in a significantly higher protein loss compared to modified cellulosic membrane. Moreover, the proteomics analysis showed that the removed proteins represented different molecular weight range and different functional groups: transport proteins, protease inhibitors, proteins with role in immune response and regulations, constructive proteins and as a part of HLA immune complex. The effect of this protein removal on hemodialysis treatment outcome should be investigated in further studies.

Biography:

Ming Jiang is pursuing his Doctor's Degree at Sun Yat-sen University. His current research is focused on the metabolic mechanism of host resistance to drug-resistant bacterial infections.

Abstract:

Antibiotic-resistant bacteria become a major threat to the economy and food safety in aquaculture. Although the antibiotic-dependent strategy is still the mostly adopted option, the development of antibiotic-free approach is urgently needed to ameliorate the severe situation of the global antibiotic resistance. In the present study, we showed that modulating the metabolism of zebrafish, Danio rerio, would enhance D. rerio to clear ceftazidime-resistant Vibrio alginoyticus (Caz-R) in vivo. By generating Caz-R in vitro, we found Caz-R stays longer than ceftazidime-sensitive V. alginoyticus (Caz-S) in D. rerio, where Caz-R induced less potent immune response than that of Caz-S. The differential immune response was associated with different metabolism of the host. Through functional metabolomics, we identified a crucial biomarker, phenylalanine. The abundance of phenylalanine was increased in both of Caz-S and Caz-R infected hosts but the abundance was higher in Caz-S infected group. This specific difference indicated phenylalanine could be a metabolite required to clear Caz-R by the host. Exogenous phenylalanine would enhance the host’s ability to remove Caz-R, which was through upregulated production of lysozyme and C3b. Thus, our study demonstrates a novel strategy to boost host’s immune response to combat against antibiotic-resistant bacteria.

Biography:

Yankai Xia is the Dean of the School of Public Health, Nanjing Medical University, Vice Director of Center for Global Health and the PI of State Key Laboratory of Reproductive Medicine and Key Laboratory of Modern Toxicology of the Ministry of Education. His current research interests are Systems Biology and Environmental Health. He has been using high-throughput techniques to profile human environmental exposure and biological responses to exogenous chemicals. He has presided over more than ten national and ministerial projects, including the State Key Program of National Natural Science Foundation of China and the National Outstanding Youth Science Foundation. He has been the committee member of several domestic and international academic organizations. He has published over 110 peer-reviewed articles, and got 7 national invention patents. He also serves as the editor and reviewer of more than 20 international journals

Abstract:

The etiology and pathogenesis of Hirschsprung’s disease (HSCR) remain largely unknown. Here we employed a multiple ‘omics’-analysis to explore the important pathway related to the development of HSCR. We examined colon tissues from three independent populations with a combined analysis of metabolomics, transcriptomics and proteomics to understand HSCR. Mouse model was used for examining PGE2 induced clinical presentation of HSCR. SH-SY5Y and SK-N-BE(2) cell lines were used for examining PGE2 inhibited cell migration through EP2.The integrated analysis suggests that the level of PGE2, the expression of the genes encoding its receptor (EP2) (PTGER2) and PGE2 synthesis enzyme genes (PTGS1 and PTGES) increased in HSCR colon tissues, together with a decreased synthesis of PGE2-related byproducts. In animal study, the pregnant mice treated with PGE2 gave birth to offspring with the lack of gangliocytes in colon and gut mobility. In vitro study, we confirmed that, when EP2 was blocked, the PGE2-inhibited migration of neural cell was recovered. Our study identified a novel pathway linking expression of PTGS1 and PTGES, level of PGE2, expression of PTGER2, and neural cell migration in HSCR, providing a novel avenue for the future diagnosis and prevention of HSCR.

Biography:

Manjun Yang is a lecturer of Tibet Vocational Technical College. He is pursuing his PhD from Sun Yat-sen University. His tutor is Prof. Xuanxian Peng who is a famous scientist of China. He has been committed to the research of bacterial antibiotic resistance. He is good at using metabolomic approaches based on GC-MS and UPLC/Q-TOF- MS platform to study drug resistance.

Abstract:

Vibrio alginolyticus is a waterborne pathogen that infects a wide variety of hosts including fish and human, and the outbreak of this pathogen can cause a huge economic loss in aquaculture. Thus, enhancing host’s capability to survive from V. alginolyticus infection is the key to fight infection and this remains still unexplored. In the present study, we established a V. alginolyticus-zebrafish interaction model by which we explored how zebrafish survived from V. alginolyticus infection. We used GC-MS based metabolomic approaches to characterize differential metabolomes between survival and dying zebrafish upon infection. Pattern recognition analysis identified the TCA cycle as the most impacted pathway. The metabolites in the TCA cycle were decreased in the dying host, whereas the metabolites were increased in the survival host. Furthermore, the enzymatic activities of the TCA cycle including pyruvate dehydrogenase (PDH), α-ketoglutaric dehydrogenase (KGDH) and succinate dehydrogenase (SDH) also supported this conclusion. Among the increased 3 metabolites in the TCA cycle, malic acid was the most crucial biomarker for fish survival. Indeed, exogenous malate promoted zebrafish survival in a dose-dependent manner. The corresponding activities of KGDH and SDH were also increased. These results indicate that the TCA cycle is a key pathway responsible for the survival or death in response to infection caused by V. alginolyticus, and highlight the way on development of metabolic modulation to control the infection.

Biography:

Ye Jinzhou is passionate about metabolic regulation of bacterial resistance. During his PhD and Postdoctoral periods, he devoted himself to studying the metabolic regulation mechanism in the process from tolerant to resistant.

Abstract:

Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remain to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS) production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.

Biography:

Katsuya Nagayama has his expertise in numerical simulation using particle model. The model was applied to express phenomena such as tumor growth, hair formation, skin turnover, alveolar bone regeneration and liver cell proliferation.

Abstract:

Introduction: Malignant tumors are difficult to observe in the growth process, and clarification of the phenomenon is desired. Gompertz model is said to apply to the growth of malignant tumors. Therefore, we aim to carry out numerical simulation of the growth process of malignancy and reproduce the model of Gompertz.

Method: Introduce particle model as a simulation method. A particle model is a numerical analysis method that uses cell clusters as particles with physical quantities and tracks the movement of particles. In the analysis procedure, first, a blood vessel network is placed in a three-dimensional area, and cancer cell group particles are randomly generated.

Calculation conditions: Blood vessels elongate and diverge according to the amount of attractant from undernourished cancer cells nearby. The amount of attractant was inversely proportional to the amount of nutrition. For nutrient transport between blood vessels and cells, the diffusion equation is used. Cancer cells with high nutrient concentration were actively divided and those with poor nutrition were dormant. We considered the killing by immune cells and the killing by internal pressure.

Results: Figure 1 shows the number of cancer cells grown over time, and Figure 2 shows the cancer status at the end of the calculation. In the early stage, proliferation is inhibited by the influence of immune cells. In the middle stage, some cancer cells that escaped from immune cells increased rapidly. In the late stage, the growth rate became slower because the malignant tumor became larger and the nutrient supply into the tumor worsened.

Conclusions: We performed numerical simulations from the onset of malignancy. It was confirmed that the number of cancer cells proliferated matched qualitatively to the Gompertz model.

Biography:

Abstract:

The work focuses on cellular redox homeostasis in prokaryotic micro-organisms, and specifically on factors associated with nicotinamide adenine cofactor [NADP(H) and NAD(H)] metabolism in E. coli and photoautotrophic cyanobacterium Synechocystis sp. PCC 6803. These cofactors participate in numerous electron transfer reactions in the cell, linking enzymatic reactions with the overall energy metabolism with biosynthetic reactions and housekeeping functions. Obtaining a comprehensive view of the interactions and the regulatory circuits is thus of central importance in understanding the adaptation to different environmental conditions, such as those involved with the transition between autotrophic and heterotrophic growth modes in cyanobacteria. The principal objective is to study the role of the proton gradient-coupled pyridine nucleotide transhydrogenase PntAB. Functional characterization combined with structral modelling of PntAB in Synechocystis sp. PCC 6803 has been carried out, and information-rich networks have been created to identify identify novel candidates involved in the NADP(H)-regulation in different organisms. In addition, PntAB is studied through deletion and over-expression mutants under anaerobic fermentative conditions and under different pH’s in E. coli. Specifically, the initiative is to elucidate to what extent the regulation of the cofactor redox balance takes place at the level of alternative catabolic routes in glucose breakdown, and what is the role of PntAB under these specific conditions. The approach is to generate pntAB over-expression and knock-out strains, and to compare them in phenotypic growth properties as well as in respect to changes in the central carbon metabolism by analyzing the distribution of local ratios of amino acids using C¹³ labelled glucose as a probe.