ME Seminar

The Mathematical Biology Laboratory of Kyushu University holds informal seminars.
Anyone who has interest in them is welcome!

Access:  Kyushu University - Ito campus (West Zone 1)

Coordinator:  Shoya Iwanami
Graduate School of Systems Life Sciences, Kyushu University,
Fukuoka 819-0395, Japan
tel +81-92-802-4299

Dissemination of multidrug resistance via conjugative plasmid.

Yoshiharu Yamaichi

Institute for Integrative Biology of the Cell (I2BC), CNRS-Gif-sur-Yvette, FRANCE

2017/11/18, 13:30-, at W1-D-923


     Wide-spreading of antibiotic resistance is one of the most important issues in not only public health but also a huge economic burden. Dissemination of multidrug resistance (MDR) gene(s) resulted in emergence of MDR bacteria, or casually called “superbugs”. These transmissions were often carried out by conjugative plasmids that also encode genes sufficient for a means of horizontal gene transfer, namely conjugation which is carried out by cell-to-cell contact. We are interested in dynamics of dissemination of MDR conjugative plasmid, using pESBL as our model plasmid. This plasmid was originally identified in Escherichia coli O104 outbreak strain in Germany in 2011, and participated the severity of outbreak as it provided MDR phenotype to the host cells.
     Taking advantage of Transposon insertion site sequencing (Tnseq), a recently developed technique which allows the high-throughput quantitative fitness assessment of individual genomic loci, we identified genes involved in the conjugative transfer of pESBL. Surprisingly, Tnseq also unveiled a small regulatory region in pESBL: mutations in this region result in highly elevated transfer efficiency of the plasmid. This and other lines of evidence indicate that single mutations can create plasmids with substantially increased ability to spread, threatening emergence of ’superspreader’ mutants.
     Transferred plasmid molecule has to be established in the recipient cell for the completion of the conjugative DNA transfer. I will also discuss our recent studies on various factors involved in this establishment, such as plasmid partitioning and a system counteracting host immunity.

The genomic landscape at the later stages of speciation: insights from Japanese sticklebacks.

Mark Ravinet

CEES, University of Oslo, Norway

2017/10/18, 15:00-, at W1-D-208


      Speciation is a continuous process and analysis of species pairs at, "different stages of divergence provides insight into how it unfolds. Spanning the speciation continuum stickleback species pairs are ideal for investigating how genomic divergence builds up during speciation. However attention has largely focused on young postglacial species pairs with little known of the genomic signatures of divergence and introgression in older systems. The Japanese stickleback species pair Gasterosteus aculeatusG. nipponicus which co-occur in the Japanese islands is at a late stage of speciation. Here we use coalescent analyses and Approximate Bayesian computation to show that the two species split approximately 0.68-1 million years ago but that they have continued to hybridise at a low rate throughout divergence. Population genomic data revealed that high levels of genomic differentiation are maintained across the majority of the genome when gene flow occurs. However despite this we identified multiple small regions of introgression strongly correlated with recombination rate. Our results demonstrate that a high level of genome-wide divergence can establish in the face of persistent introgression and that gene flow can be localized to small genomic regions at the later stages of speciation with gene flow, composed of the Pacific Ocean three-spined stickleback and the Japan Sea stickleback.

Linking biodiversity, ecosystems, and people across scales: challenges for ecology and sustainability.

Michel Loreau

Centre for Biodiversity Theory and Modelling, Theoretical and Experimental Ecology Station, UMR 5321 CNRS and Paul Sabatier University, France

2017/10/18, 15:00-, at W1-D-208


      People are now driving the sixth mass extinction in Earth’s history, and yet biodiversity enhances many of nature’s benefits to people. The influence and dependence of people on biodiversity have mainly been studied separately and at contrasting scales of space and time but new ecological theory is beginning to link these relationships across scales. This theory shows that biodiversity loss substantially diminishes many ecosystem services by altering ecosystem functioning and stability especially at the large temporal and spatial scales that are most relevant for policy and conservation. The influence and dependence of people on biodiversity also generate an important if poorly understood feedback loop between humans and nature. New models of social-ecological systems emphasize the role of feedbacks and scales in human-nature interactions and the importance of foresight for the sustainability of human societies. They call for the development of integrative management approaches that account for the coupled dynamics of human populations biodiversity and ecosystems across multiple spatial and temporal scales.

Eco-evolutionary feedback between size and strategy; alternative migratory tactics in salmonid.

Junnosuke Horita1 and Yuuya Tachiki1,2

1Kyushu University
2Department of Animal and Plant Sciences, The University of Sheffield, UK

2017/10/03, 13:30-, at W1-C-909


     In salmonids, some juveniles migrate to the ocean and come back to their natal river (migrant tactic), whereas others mature in the river without migration (resident tactic). There is a trend that larger one becomes a resident. This trend is explained by the status-dependent-strategy model(SDS), in which fitness functions of both tactics are functions of status, and the status where both fitness functions intersect is a threshold at which tactic changes. A density dependence of growth is documented. We incorporate the growth suppression of juveniles into the SDS, and explore how it affects the dynamics of alternative tactics. In this talk, we demonstrate that the negative feedback between resident density and juvenile body size can cause an instability of size distribution of juvenile, resulting in a fluctuation of the population density of migrant type as well as stream population. We also consider the effect of climate change on the average body size of juvenile, and investigate the ecological and evolutionary response to it. As a result, change in the average size can cause phase transition from stable to unstable and vice versa. Evolutionary response to the change can recover the state of population to the same state before environmental change, but various type of dynamics emerged during evolutionary response.

Advantage of sexual reproduction resulting from sibling diversity: the effects of selection intensity, environmental variance, and reduced genetic diversity.

Makoto Douge1 and Yoh Iwasa1

1Kyushu University

2017/09/26, 13:30-, at W1-C-909


     The reason of why sexual reproduction has been maintained is a big question. About forty years ago Maynard Smith presented a concept of "two-fold cost of sex. Since then many hypotheses have been submitted. However the general answer has not been found yet. One of the hypotheses showed that the diversity of siblings was the cause (Lottery Hypothesis, Williams). Maynard Smith investigated it by computer simulation called "sib-competition model". He resulted that in the model the diversity of siblings was not able to overtake the two-fold cost of sex. Currently it is almost neglected. We revised the sib-competition model to shows the force that surpasses the two-fold cost. Further, we added the following three factors in the model to get closer to the reality: [1] milder selection, [2] environmental variance (VE), [3] reduced number of phenotypes. The result showed the advantage of sexual reproduction in some probable conditions. We think that the diversity of siblings may have the important roll for the big question.

Mathematical modeling of oncolytic virotherapy in combination with chemotherapy.

Kwang Su Kim1, Jungmin Lee1, Sangil Kim2,* and Il Hyo Jung1

1Department of Mathematics, Pusan National University, Busan, 609-735, South Korea
2WISE Institute, Hankuk University of Foreign Studies, 156-849, South Korea

2017/7/25, 13:30-, at W1-C-909


      Over the past few years, several studies have been made on cancer viral therapy. One of the major advantages of oncolytic virotherapy over standard cytotoxic chemotherapeutic agents is that tumor cell selectivity can potentially target and eliminate cancer cells without affecting normal cells. Therefore studies of the virus dynamics are needed for the purpose of cancer treatment, not the virus as the cause of the disease.
     We introduce a deterministic and stochastic model of tumor-viral dynamics. For finding conditions of virotherapy failure, the local asymptotic stability and the global asymptotic stability of a virotherapy failure equilibrium are studied. By using the basic reproductive ratio, we investigate its sensitivity to the parameter values characterizing viruses. We also derive a system of stochastic differential equations that based on the deterministic model and explore the probability of uninfected tumor and infected tumor extinction. The analysis suggests that an oncolytic virus is desired with a high infection rate and optimal cytotoxicity for effective treatment. Recent investigators showed that the combination of viral therapy with chemotherapy may lead to synergistic mechanisms for eliminating cancer not achievable by either therapy alone. So our main problems are “Which combination therapy should we take for more effective treatment?” and “How can we measure and predict the quantity of synergy effect?”. Koizumi and Iwami suggested the estimation methods of the optimal dose point that is calculated from the difference between the effects of the combined drugs obtained by modeling the dynamics and the additive effects by Loewe additivity. Based on their ideas, we investigate a synergistic effect between oncolytic virus therapy and chemotherapy. Extended synergy concepts for combination therapy are discussed.


勝原光希, 丑丸敦史


2017/7/4, 13:30-, at W1-C-909


      発表者は、同所的に分布する在来一年生草本2品種、ツユクサCommelina communisとケツユクサC. communis f. cliataにおいて、非対称的な繁殖干渉が発生していること(ツユクサがケツユクサより繁殖干渉において優位)、その非対称性がツユクサがケツユクサよりも高い先行自家受粉率を持っていることによって説明されること、を明らかにしてきた。それらの結果から、通常先行自家受粉が進化しない(送粉者制限がない・遅延自家受粉ができる)場合でも、送粉者を介した種間競争が存在する場合には先行自家受粉が進化するという仮説を立て、個体ベースモデルシミュレーションを用いて検証を行ったので、その結果について紹介する。

Allergen immunotherapy as a treatment of pollen allergy, and possible coupling with intestinal microbe community dynamics.

Akane Hara and Yoh Iwasa

Kyushu University

2017/6/27, 13:30-, at W1-C-909


      Allergen immunotherapy is a treatment method for Japanese cedar pollen allergy (JCPA). Patients suffer symptoms such as runny noses and itchy eyes in pollen season often early spring in Japan. In the therapy, patients take in a small amount of pollen extract dose for several years and their allergic symptoms are suppressed when exposed to large amount of environmental pollen. However, the therapy is not always effective for all the patients of JCPA.
      To reveal conditions in which the therapy is effective, we developed simple mathematical model of allergen immunotherapy describing the differentiation process of Th2 cells (type 2 helper T cells; trigger of allergy) and Treg cells (regulatory T cells; suppressor of allergy). We found conditions for therapeutic success as follows: [1] Treg cells must have a low decay rate in order to achieve accumulation during therapy phase, and [2] therapy schedule with a longer "induction phase" in which patients have gradually increasing pollen dose with time is more effective in suppressing allergy by exposure to environmental pollen without symptoms caused by the therapy itself.
      Recently, close relation between human immune system and intestinal microbes has been known, and the effect of a particular group of bacteria on avoiding development of allergy has been reported. In this seminar, I will discuss a possible extension of the allergen immunotherapy model to a coupled immune-enterobacteria dynamics.

Number of infection events per cell during HIV-1 cell-free infection.

Yusuke Ito

Kyushu University

2017/2/14, 13:30-, at W1-C-909


      Human Immunodeficiency Virus type 1 (HIV-1) accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Although the heterogeneity of target cell susceptibility was proposed as a possible mechanism for the non-randomness, the quantitative evaluation of its impact on coinfection frequency is lacking, especially for cell-free infection in vitro.
     Here, we developed a novel mathematical model considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our novel model reproduces these datasets. Furthermore, our quantitative analyses reveal that the average number of infection events increases from 1.02 to 1.65 as the amount of inoculated HIV-1 increases, and the multiple infection frequency increases to 17%. These findings demonstrate that cell-free HIV-1 infection has an important role in driving virus recombination. Therefore, spatially separated HIV-1 variants from different organs might be able to recombine within patients via cell-free infection.

Mathematical model of hematopoietic system with myeloid bypass.

Shoya Iwanami

Kyushu University

2017/2/7, 13:30-, at W1-C-909


      The conventional model of hematopoiesis has hierarchical structure and it is considered that all blood cells produced through multi-potent progenitors (MPPs). Recently, many researches about hematopoietic stem cells (HSCs) implied the differentiation of HSC incline to produce myeloid cells. Furthermore, Yamamoto et al (2013) showed the existence of some cells producing only myeloid cells in HSC fraction and proposed a new model of hematopoiesis which has the bypass which produce myeloid cells from the stage of the stem cell.
      In our study, we developed the mathematical model based on myeloid bypass model and analyzed the data from an experiment of single cell transplantation using mice. From result of analysis, we discuss the existence and the significance of the myeloid bypass.

Evolution of density-dependent wing determination that is regulated by juvenile hormone level.

Takahiro Kamioka

Kyushu University

2017/1/31, 13:30-, at W1-C-909


      We studied the evolution of juvenile hormone (JH) regulation in wing-polymorphic insects. We considered an asexual species that undergo larval and adult stages living in many patches. The rate of larval growth depends on within-patch resources which can be depleted by larvae. Dispersal-type adults migrate out of the natal patch just before reproductive stage; reproductive-type adults have a greater fertility than those of dispersal-type adults but no dispersal ability. The wing type was determined by the juvenile hormone (JH) level in a critical period if the larval stage. The carrying capacity of resources fluctuates between high and low values. The JH level follows a normal distribution. Evolution modifies the mean and the variance of JH level. The mean of JH level is determined by the basal JH level and density dependent degradation. The variance of JH level is constant.
      First, we calculated when the mean and the variance of the JH level were evolved separately. In the evolution of mean of JH level, both of the basal JH level and density response affected the dispersal type production. In the evolution of variance of JH level, the variance evolved smaller when the environmental fluctuation was large. In both cases, the production of dispersal type was small if the density was low, and it increased rapidly if the density was large. The production of dispersal type was larger when the environmental fluctuation was larger. The growth rate and mortality of insects, and recovery of resources also affected the dispersal type production. Second, we calculated when the mean and the variance of the JH level were evolved simultaneously. When the environmental fluctuation was large, the variance was converged into minimum value. When the environmental fluctuation was small, all of these values affected the wing determination.