Conferences & Workshops

Frontiers in Single Cell Biology – SBP’s 38th Annual Symposium
Tuesday, October 10, 2017
9:00 am – 5:00 pm
Hilton Torrey Pines
Hosted by Drs. Peter Adams and Sumit Chanda
Register for the event here

SDCSB’s Quarterly Systems-to-Synthesis Meeting (Fall 2017)
Wednesday, November 1, 2017
2:00 – 5:00 pm
UC San Diego, Medical Education Telemedicine Bldg, 141-143
Registration begins fall 2017

Ensembl Tutorial
Thursday, January 11, 2018
8:30 am – 4:30 pm
UC San Diego, MET Bldg, Room 141
Hosted by Helen Sparrow – Ensembl Outreach Officer
European Bioinformatics Institute (EMBL-EBI)
Registration begins winter 2017

SDCSB’s Quarterly Systems-to-Synthesis Meeting (Spring 2018)
Thursday, May 17, 2018
2:00 – 5:00 pm
UC San Diego, Medical Education Telemedicine Bldg, 141-143
Registration begins spring 2018

 

Weekly Events

Genetics, Bioinformatics and Systems Biology Colloquium (2016-17)

qBio Seminar Series (2016-17)

Systems Biology Career Development Seminars (Spring 2017)

Monthly Events

San Diego Bioinformatics Users Series (SDBUS)

Systems Biology Club

Cell-Cell Communication and Heterogeneity

Investigators: Gurol Suel, Roy Wollman

Understanding the emergent properties of tissue-level organization is a fundamental problem in biology. These properties emerge from the many different interactions of individual cells within a tissue. Yet, there are no methods that use the spatial distribution of cells and their signaling state to build a computational model that can make specific, testable predictions on tissue-level phenotypes. In this project we will use the maps-to-models paradigm to study two models of biological  tissue organization: (1) antibiotic resistance of a biofilm of Bacillus subtilis; and (2) induction of viral protection through type I interferon response in lung epithelial cells during influenza infection. Through the use of two separate model systems we will demonstrate the utility of our approach and show how it could be further adapted to the analysis of tissue-level biological organization.

A key benefit of the Maps-to-Models paradigm is the generation of two interdependent deliverables: (1) a map depicting interactions (edges) between building blocks (node); and (2) a computational model generating testable predictions on the functional output of the network. In this project, the basic biological unit is the cell. We will generate detailed, quantitative network maps characterizing heterogeneous cells within a tissue and their communication network. Cells states will be determined by analyzing the signaling states of each individual cell. The interaction network between individual cells depends on their strength of paracrine communication. An edge will connect any two sender and receiver cells within the tissue and the weight of the edge will denote the strength of the diffusion limited communication. The two maps generated by this project will provide information on the spatiotemporal organization of bacillus biofilms and epithelium barriers and the extent of cell-to-cell communication within these tissues. These maps will be used to develop quantitative, predictive models.

One part of this project will focus on the emergence of antibiotic resistance during biofilm formation of B. subtilis strain NCIB-3610. Numerous genes involved in biofilm formation have been identified in this strain, and, as a result, much of our understanding of biofilm formation was obtained in this model system. Despite this wealth of information, many fundamental questions remain unaddressed. The Suel laboratory has developed extensive expertise in quantitative measurements and genetic manipulation of NCIB-3610 (Asally et al., Proc Natl Acad Sci U S A 2012) including the use of multicolor fluorescence microscopy to simultaneously measure the activities of multiple intracellular processers in individual cells (Cagatay et al., Cell 2009. Fluorescent proteins and reporter dyes with distinct spectral will be used to track specific molecules and reactions in B. subtilis. These fluorescent reagents will be tracked using our fully automated, multicolor fluorescence time-lapse microscopy systems, which also provide temperature, humidity and gas control. Having tested many microscope objectives, we have identified special long distance objectives that are capable of measuring  biofilms over a centimeter in diameter. We have also developed custom software, which can quantify microscopy images to track cell lineages or other movements within biofilms.  
 
 
 
 

The second part of this project will focus on the epithelium, a critical barrier that protects our bodies from infections by harmful pathogens. Communication between cells within the epithelium is important for initiating and managing innate immune responses. It is not clear though how the epithelium balances generating enough of an immune response to combat the pathogen while not damaging itself. One possible mechanism is that individual cellular responses are stochastic and might thus determine the extent of cell-to-cell communication. Previously, the Wollman laboratory explored the role of stochastic cellular responses during NF-κB signaling in response to LPS (Selimkhanov et al., Science 2014). In the course of this work, we developed a suite of computational tools capable of automatically analyzing fluorescent microscopy images for nuclear and cytoplasmic levels of p65, a subunit of NF-κB subunit. In this project, we will continue to study this pathway, using p65 translocation as readout of cellular response to viral infection.  
 
 
 
 
 
 

 

Recent Publications by these New SDCSB Investigators:

  1. Wollman, R. Single-Molecule Threshold of HIV Fate Decision. Biophys. J. 2017;112 (11):2247-2248. doi: 10.1016/j.bpj.2017.03.041. PubMed PMID:28591597 .
  2. Handly, LN, Wollman, R. Wound-induced Ca(2+) wave propagates through a simple release and diffusion mechanism. Mol. Biol. Cell. 2017;28 (11):1457-1466. doi: 10.1091/mbc.E16-10-0695. PubMed PMID:28404746 PubMed Central PMC5449146.
  3. Liu, J, Martinez-Corral, R, Prindle, A, Lee, DD, Larkin, J, Gabalda-Sagarra, M et al.. Coupling between distant biofilms and emergence of nutrient time-sharing. Science. 2017;356 (6338):638-642. doi: 10.1126/science.aah4204. PubMed PMID:28386026 .
  4. Humphries, J, Xiong, L, Liu, J, Prindle, A, Yuan, F, Arjes, HA et al.. Species-Independent Attraction to Biofilms through Electrical Signaling. Cell. 2017;168 (1-2):200-209.e12. doi: 10.1016/j.cell.2016.12.014. PubMed PMID:28086091 .
  5. Yao, J, Pilko, A, Wollman, R. Distinct cellular states determine calcium signaling response. Mol. Syst. Biol. 2016;12 (12):894. . PubMed PMID:27979909 PubMed Central PMC5199124.
  6. Handly, LN, Yao, J, Wollman, R. Signal Transduction at the Single-Cell Level: Approaches to Study the Dynamic Nature of Signaling Networks. J. Mol. Biol. 2016;428 (19):3669-82. doi: 10.1016/j.jmb.2016.07.009. PubMed PMID:27430597 PubMed Central PMC5023475.
  7. Prindle, A, Liu, J, Asally, M, Ly, S, Garcia-Ojalvo, J, Süel, GM et al.. Ion channels enable electrical communication in bacterial communities. Nature. 2015;527 (7576):59-63. doi: 10.1038/nature15709. PubMed PMID:26503040 PubMed Central PMC4890463.
  8. Handly, LN, Pilko, A, Wollman, R. Paracrine communication maximizes cellular response fidelity in wound signaling. Elife. 2015;4 :e09652. doi: 10.7554/eLife.09652. PubMed PMID:26448485 PubMed Central PMC4686426.
  9. Liu, J, Prindle, A, Humphries, J, Gabalda-Sagarra, M, Asally, M, Lee, DY et al.. Metabolic co-dependence gives rise to collective oscillations within biofilms. Nature. 2015;523 (7562):550-4. doi: 10.1038/nature14660. PubMed PMID:26200335 PubMed Central PMC4862617.
  10. Zhang, F, Kwan, A, Xu, A, Süel, GM. A Synthetic Quorum Sensing System Reveals a Potential Private Benefit for Public Good Production in a Biofilm. PLoS ONE. 2015;10 (7):e0132948. doi: 10.1371/journal.pone.0132948. PubMed PMID:26196509 PubMed Central PMC4510612.
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