[IBS 의생명 수학 그룹] 10월 세미나
글쓴이 : KSIAM
작성일 : 2021-10-05

ZOOM ID: 709 120 4849 (ibsbimag) (pw:1234)

https://www.ibs.re.kr/bimag/event/2021-10-07/


A temporal signaling code to specify immune responses

SPEAKER : Alexander Hoffmann https://www.signalingsystems.ucla.edu/alexander-hoffmann/


This talk will be presented online. Zoom link: 709 120 4849 (pw: 1234)

Date&Time: October 7 @ 11:00 am - 12:00 pm KST ZOOM


Abstract: Immune sentinel cells must initiate the appropriate immune response upon sensing the presence of diverse pathogens or immune stimuli. To generate stimulus-specific gene expression responses, immune sentinel cells have evolved a temporal code in the dynamics of stimulus responsive transcription factors. I will present recent works 1) using an information theoretic approach to identify the codewords, termed “signaling codons”, 2) using a machine learning approach to characterize their reliability and points of confusion, and 3) dynamical systems modeling to characterize the molecular circuits that allow for their encoding. I will present progress on how the temporal code may be decoded to specify immune responses. Further, I will discuss to what extent such a code may be harnessed to achieve greater pharmacological specificity when therapeutically targeting pleiotropic signaling hubs.


Organizer : Jae Kyung Kim (jaekkim@kaist.ac.kr)


ZOOM ID: 709 120 4849 (ibsbimag) 

https://www.ibs.re.kr/bimag/event/2021-10-21/


Scaling in development

SPEAKER : Chao Tang

Peking University http://cqb.pku.edu.cn/tanglab/index.php?lang=en


This talk will be presented online. Zoom link: 709 120 4849 (pw: 1234)

Date&Time: October 21 @ 11:00 am-12:00 pm KST


Abstract: Within a given species, fluctuations in egg or embryo size is unavoidable. Despite this, the gene expression pattern and hence theembryonic structure often scale in proportion with the body length. This scaling phenomenon is very common in development andregeneration and has long fascinated scientists. I will first discuss a generic theoretical framework to show how scaling geneexpression pattern can emerge from non-scaling morphogen gradients. I will then demonstrate that the Drosophila gap gene systemachieves scaling in a way that is entirely consistent with our theory. Remarkably, a parameter-free model based on the theoryquantitatively accounts for the gap gene expression pattern in nearly all morphogen mutants. Furthermore, the regulation logic andthe coding/decoding strategy of the gap gene system can be revealed. Our work provides a general theoretical framework on a largeclass of problems where scaling output is induced by non-scaling input, as well as a unified understanding of scaling, mutants’behavior and regulation in the Drosophila gap gene and related systems.


Organizer : Jae Kyung Kim (jaekkim@kaist.ac.kr)


ZOOM ID: 709 120 4849 (ibsbimag) 

https://www.ibs.re.kr/bimag/event/2021-10-27/


Systems pharmacology towards personalized chronotherapy

SPEAKER : Annabelle Ballesta INSERM http://annabelle.ballesta.fr/

 

This talk will be presented online. Zoom link: 709 120 4849 (pw: 1234)

Date&Time: October 27 @ 5:00 pm - 6:00 pm KST


Abstract: Chronotherapeutics- that is administering drugs following the patient’s biological rhythms over the 24 h span- may largely impact on both drug toxicities and efficacy in various pathologies including cancer [1]. However, recent findings highlight the critical need of personalizing circadian delivery according to the patient sex, genetic background or chronotype. Chronotherapy personalization requires to reliably account for the temporal dynamics of molecular pathways of patient’s response to drug administration [2]. In a context where clinical molecular data is usually minimal in individual patients, multi-scale- from preclinical to clinical- systems pharmacology stands as an adapted solution to describe gene and protein networks driving circadian rhythms of treatment efficacy and side effects and allow for the design of personalized chronotherapies. Such a multiscale approach is being undertaken for personalizing the circadian administration of irinotecan, one of the cornerstones of chemotherapies against digestive cancers. Irinotecan molecular chronopharmacology was studied at the cellular level in an in vitro/in silico investigation. Large transcription rhythms of period T= 28 h 06 min (SD 1 h 41 min) moderated drug bioactivation, detoxification, transport, and target in synchronized Caco-2 colorectal cancer cell cultures. These molecular rhythms translated into statistically significant changes according to drug timing in irinotecan pharmacokinetics, pharmacodynamics, and drug-induced apoptosis. Clock silencing through siBMAL1 exposure ablated all the chronopharmacology mechanisms. Mathematical modeling highlighted circadian bioactivation and detoxification as the most critical determinants of irinotecan chronopharmacology [3]. The cellular model of irinotecan chronoPK-PD was further tested on SW480 and SW620 cell lines, and connected to a new clock model to investigate the feasibility of irinotecan timing personalization solely based on clock gene expression monitoring (Hesse, Martinelli et al., under review). To step towards the clinics, on one side, mathematical models of irinotecan, oxaliplatin and 5-fluorouracil pharmacokinetics were designed to precisely compute the exposure concentration of tissue over time after complex chronomodulated drug administration through programmable pumps [4]. On the other side, we aimed to design a model learning methodology predicting from non-invasively measured circadian biomarkers (e.g. rest-activity, body temperature, cortisol, food intake, melatonin), the patient peripheral circadian clocks and associated optimal drug timing [5]. We investigated at the molecular scale the influence of systemic regulators on peripheral clocks in four classes of mice (2 strains, 2 sexes). Best models involved a modulation of either Bmal1 or Per2 transcription most likely by temperature or nutrient exposure cycles. The strengths of systemic regulations were found to be significantly different according to mouse sex and genetic background.


Organizer : Jae Kyung Kim (jaekkim@kaist.ac.kr)