4/3 – BioMath Joint Lunch

When: Tuesday, 4.3.2014  12:00

Where:  The lawn between Britanya and Schreiber

We will have a joint lunch with the Theoretical Biology Masters program.

If you want to spend an hour with other people who are also interested in math and biology, this is your chance!

Bring your own food and drink.

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BioMath joint Lunch/Brunch

Eli Levy Karin is organizing a meeting for everyone interested in BioMath at Tel-Aviv University. Here is her message:

“Hello all,

Would you like to have a joint Lunch/Brunch get together some time in the next two weeks?
I thought this could be a nice opportunity to get to know each other.

In order to make things simple(r), I think the best way to do it is in campus and each will be responsible for their own food+drink.

If you’re interested, please enter the dates and times possible for you in this doodle survey:
http://doodle.com/tvb273p9qbighnhs

If you know of BioMath club members who are missing from this email, please forward this to them.

Good luck to us all in the upcoming semester!”

Please go to the above link and put in your prefered time and date.
We could also use that opportunity to talk about the future of the BioMath Student Journal Club that has been rather silent lately.

31/7 – How to learn an experiment?

When: Wednesday, 31.7.2013  14:00

Where:  Katzir Club (Green Bldg)

Speaker: Nir Atias (CS, TAU)

Boolean networks are powerful models of cell signaling. However, the sparsity of currently available data, allows many different models to explain this data equally well. Obviously, we need more experiments and more data, but devising such informative experiments may not be trivial. We compared several alternatives and developed an algorithm to learn, de-novo, such experiments. We show that using such formal methods on simulated and real data improve on random selection. We also show that current data sets include redundant experiments and could be improved using our design methods.

12/6 – Gradual and catastrophic regime shifts

When: Wednesday, 12.6.2013  15:00

Where:  Katzir Club (Green Bldg)

Speaker: Yuval Zelnik (Meron Lab, BGU)

Climatic changes and man-made disturbances can bring about various regime shifts in ecosystems, such as a desertification process or complete collapse of a productive system. These shifts are often seen as catastrophic (irreversible and abrupt), due to an inherent bi-stability in the system that leads to a hysteresis scenario. In spatially extensive systems however, this view is often an over-simplification of reality, as several spatial scales lead to different patterns in the system, and to richer dynamics.
We study 4 such models that exhibit vegetation patchiness due to feedbacks between water and plants, and focus in particular on the results of the simplified Gilad model. We argue that the classic view of bi-stability does not fully capture the possible states of the system, due to multiplicity of pattern wavelength, and the occurrence of localized states in the system. Further, we do not find evidence of the possibility of an invasion of a bare-soil state front, i.e., expansion of the bare-soil into the patterned area, in any of the models studied. These finds lead us to consider the occurrence of desertification as a process of front dynamics or gradual transition. We also look at a system with a bi-stability of gaps pattern and uniform vegetation, and ask how the results of this system relate to the dynamics of so called “Fairy Circles” in Africa.

3/4 – Design principles of altruistic behavior

When: Wednesday, 3.4.2013  15:00

Where:  Katzir Club (Green Bldg)

Speaker: Ishay Ben-Zion (Eldar lab, TAU)

 

Many theoretical studies in the last 50 years have tried to explain the evolutionary maintenance of altruistic behavior in the face of exploitive cheaters. It is well known that a strong population structure is crucial for the maintenance of altruistic cooperation. However, it is unclear how this requirement is affected by the regulatory structure of the cooperative trait. The aim of this work is to examine the role of feedback regulation in maintaining cooperation in a public goods model. Our results suggest an important advantage of positive feedback regulation over negative or no feedback: a positive-feedback structure promotes cooperation in weaker population structures as well, thus relieving a major limitation of explaining altruism. These results demonstrate that social traits may have different design principles than non-social traits. Moreover, since bacterial cooperative traits are often feedback-regulated through sensory mechanisms, elucidating the role of feedbacks may lead to experimentally amenable predictions.

13/3 – Modeling of cytomegalovirus viral kinetic patterns and clinical implications

When: Wednesday, 13.3.2013  15:00

Where:  Katzir Club (Green Bldg)

Speaker: Dr. Jessica Rose (Bar Ilan University)

The herpes virus CMV has co-evolved with humans over many millennia and is well adapted to the immunocompetent host.  However, in a variety of immune deficient hosts including the neonate, organ transplant recipients, patients with common variable immune deficiency and HIV-infected patients, the virus can cause life-threatening pathologies.  The synthetic nucleoside analogue Ganciclovir (GCV) has become the antiviral drug of choice for controlling CMV infection and disease.  The drug requires initial phosphorylation by the viral kinase UL97: an orthologue of the cellular cyclin-dependent kinases family which performs a variety of roles in the viral life cycle. Using frequent CMV load measurements over the course of 21 days of GCV therapy, we show that novel viral decay patterns are apparent in a large percentage of individuals (>60%) that cannot be explained by conventional viral dynamic models.  We therefore developed a novel 7-dimensional dynamic model that includes an intracellular feedback loop between UL97 and GCV which adequately describes the unique kinetic patterns of CMV decline observed in patients following exposure to therapy.  This has vital clinical, pharmaceutical and general scientific implications as the link between the unique viral kinetics and mode-of-action of GCV has never been reported.

28/1 – Modeling the handicap principle?

When: Monday,  28.1.2013  14:00

Where:  Katzir Club (Green Bldg)

Speaker: Keith Harris (TAU)

Since Zahavi [1] suggested the handicap principle, there have been many attempts to produce a formal mathematical model to understand whether costly signaling is an evolutionarily stable strategy (ESS). Maynard Smith [2] initially rejected the handicap principle, however, his model assumed that the handicap is a gene that is inherited and causes a loss in fitness in males who carry the handicap gene. In 1990, Grafen [3] published the first ESS model of the handicap principle, but his model assumed that the signaling parties must have a conflict of interest to necessitate reliable signaling, such as the conflict of interest between males competing for mates. This assumption contradicts Zahavi’s claim that the handicap principle is necessary even between isogenic cells in multicellular organisms [4], a claim later modeled by Krakauer and Pagel [5]. I will present the original models of Maynard Smith and Grafen, along with the more recent criticism of Számadó [6] and Zollman et al. [7], all the while focusing on the biological significance of the assumptions of each model.

References:

[1] Zahavi, Amotz. Mate selection—a selection for a handicap. Journal of theoretical Biology 53.1 (1975): 205-214.

[2] Maynard Smith, John. Sexual selection and the handicap principle. Journal of Theoretical Biology 57.1 (1976): 239-242.

[3] Grafen, Alan. Biological signals as handicaps. Journal of theoretical biology 144.4 (1990): 517-546.

[4] Zahavi, Amotz. The fallacy of conventional signalling. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 340.1292 (1993): 227-230.

[5] Krakauer, David C., and Mark Pagel. Selection by somatic signals: the advertisement of phenotypic state through costly intercellular signals. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 351.1340 (1996): 647-658.

[6] Számadó, Szabolcs. The cost of honesty and the fallacy of the handicap principle. Animal Behaviour 81.1 (2011): 3-10.

[7] Zollman, Kevin JS, Carl T. Bergstrom, and Simon M. Huttegger. Between cheap and costly signals: the evolution of partially honest communication. Proceedings of the Royal Society B: Biological Sciences 280.1750 (2013).

21/1 – The lifetime of synaptic intermediates during the search for homology on DNA

When: Monday,  21.1.2013  14:00

Where:  Katzir Club (Green Bldg)

Speaker: Adam Mani (Joel Stavans Lab, Weizmann)

Homologous recombination plays central roles in DNA repair and in the generation of genetic diversity in organisms from bacteria to man. At the heart of this process, a segment of DNA in the genome is replaced by a new one. In order for strand exchange to occur, a single-stranded DNA-recombinase complex must locate a homologous target among a large number of sequences on a genome. The search must be completed within physiologically relevant timescales, and a key element in this search is the synapse lifetime, i.e. the time needed for a comparison of the sequences in one iteration of the search. In this work, we visualized fluorescently tagged individual synapses formed by RecA, a prokaryotic recombinase, and measured their lifetime as a function of synapse length and differences in sequence between the participating DNAs. Surprisingly, lifetimes can be ~10 s long when the DNAs are fully heterologous, and much longer for partial homology. These results suggest the need for facilitated homology search mechanisms for the search to be completed within the timescales required in vivo.

 

References:

 Mani A et al  Caught in the Act: the Lifetime of Synaptic Intermediates During the Search for Homology on DNA , Nucleic Acids Research, 38:6, 2036–2042 (2010).

24/12 – De Bruijn meets DNA

When: Monday,  24.12.2012  12:00 noon (not at 14:00 as was previously published)
Where:  Britannia 202 (Map)
Speaker: Yaron Orenstein (TAU)

Utilizing reverse complementarity to efficiently cover all k-mers, with application to protein binding microarrays

Protein binding micorarrays are a novel technology that measures binding intensity of a protein to thousands of short double stranded DNA sequences called probes. By using probes that cover all k-mers, a comprehensive picture of the binding spectrum is obtained.
Space constraints limit the number of probes that can be put on an array. The standard way to create the probes is by using a de Bruijn sequence, which contains every k-mer exactly once.
Here we show that by utilizing the reverse complementarity of DNA we can create a sequence that is much shorter with the property that it contains each k-mer or its reverse complement. The obtained saving factor is near optimal and approaches 2 as k increases. This allows generation of protein binding microarrays with more effective coverage.
Keywords:  de Bruijn sequence, de Bruijn graph, Euler tour

3/12 – Measuring collective tumor cell migration

When: Monday,  3.12.2012  12:00 noon

Where:   Britannia 202 (Map)

Speaker: Assaf Zaritsky (TAU)

Collective cell migration plays a major role in many essential biological processes. Understanding the molecular and cellular mechanisms of this migration mode is limited despite decades of extensive investigations.
A set of quantitative measures, based on live cell imaging is presented, to demonstrate enhanced analyses of collective cell motility in a high throughput manner. The toolbox includes multicellular segmentation, motion estimation and tracking, motion in clusters, and measures for cells’ individuality, indirect morphology and spatiotemporal motility and visualization.
The subject matter studied is induction of collective tumor cell migration by Hepatocyte Growth Factor / Scatter Factor (HGF/SF) – Met-signalling, master regulators of cell motility in normal and malignant processes. HGF/SF-Met-signalling dramatically alters the morphokinetic dynamics of collective migration of breast cancer tumor cells by increasing cells’ orientation and cooperation capabilities. Met-inhibition reduces these phenomena.
Exploiting these high-throughput phenotyping capabilities revealed that HGF/SF signalling induced metabolic plasticity of the cells altering from glycolysis to oxidative phosphorylation thus increasing collective cell motility. However a profound inhibition of hexokinase activity significantly reduces it.
Another application was to investigate cells that maintain amoeboid-like motility while traversing in a tissue consisting of epithelial cells, as a simple model for initial metastasis formation. Low concentrations of exogenous YFP- WT-Met, activating and inhibitory forms, were expressed in a monolayer of tumor cells to simulate the phenomenon. Activating Met-variants are generally characterized by cells’ amoeboid-like motility; Met-inhibition induces epithelial motility, while HGF/SF-induces increased individuality, a measure for the motility of transfected cells in relation to their vicinity of untreated cells.
The findings reported here are anticipated to shed light on the molecular and cellular alterations that enable metastasis formation in breast cancer and hence to aid in identifying new targets for therapy.

References: