לוח שנה משולב

Cell-free circulating DNA (cfDNA), released from dying cells, is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. We developed a method of detecting tissue-specific cell death in humans, based on tissue-specific methylation patterns of DNA circulating in plasma. We interrogated tissue-specific methylome datasets to identify cell type-specific DNA methylation signatures, and established a method to detect these in mixed DNA samples and in cfDNA isolated from plasma. Using this new type of biomarker it is possible to detect the presence of cfDNA fragments derived from multiple tissues in healthy individuals and in pathologies including cancer, myocardial infarction, sepsis, neurodegeneration and more. In the long run we envision this approach opening a minimally-invasive window for monitoring and diagnosis of a broad spectrum of human pathologies, as well as better understanding of normal tissue dynamics.

Understanding how social influence shapes biological processes is a central challenge in contemporary science, essential for achieving progress in a variety of fields ranging from the organization and evolution of coordinated collective action among cells, or animals, to the dynamics of information exchange in human societies. Using an integrated experimental and theoretical approach I will address how, and why, animals exhibit highly-coordinated collective behavior. I will demonstrate new imaging and virtual reality (VR) technology that allows us to reconstruct (automatically) the dynamic, time-varying sensory networks by which social influence propagates in groups. This allows us to identify, for any instant in time, the most socially-influential individuals, to reveal the (counterintuitive) relationship between network structure and social contagion, and to predict the magnitude of complex behavioural cascades within groups before they actually occur. By investigating the coupling between spatial and information dynamics in groups we also demonstrate that emergent problem solving is the predominant mechanism by which mobile groups sense, and respond to complex environmental gradients. Finally I will reveal the critical role uninformed, or unbiased, individuals play in effecting fast, democratic consensus decision-making in collectives, and will test these predictions with experiments involving schooling fish and wild baboons, as well as suggest how such results may relate to decision-making in neural systems.

The Fisher KPP equation describes the growth of a stable region into
an unstable medium.
It was introduced in 1937 both by the biologist and statistician
Fisherand by the mathematicians Kolmogorov, Petrovsky, Piscounov to describe the propagation of a favorable gene in a population.
It is one of the classical examples of the problem of velocity selection. It also appears in many other contexts, ranging from the theory of disordered systems and spin glasses to reaction diffusion problems, branching Brownian motion and models of evolution with selection.
This talk will try to review the main classical results on this equation as well as some recent progress.

Department of Chemistry & Grossman Institute of Neuroscience and Quantitative Biology
The University of Chicago

DNA can be self-assembled into molecularly precise, well-defined, synthetic assemblies on the nanoscale, commonly referred to as designer DNA nanodevices. My lab creates synthetic, chemically responsive, DNA-based fluorescent probes. (1) In 2009 my lab discovered that these designer nanodevices could function as fluorescent reporters to quantitatively image ions in real time in living systems. (2,3) Until this innovation, it was not at all obvious whether such DNA nanodevices could function inside a living cell without being interfered with, or interfering with, the cells own networks of DNA control (4). In this talk I will discuss unpublished work on how we have expanded this technology from ion imaging (5,6) to now quantitatively imaging reactive species as well as enzymatic cleavage with sub-cellular spatial resolution in vivo.

References:

1. Chakraborty, K., et al., Nucleic acid based nanodevices in biological imaging. Ann. Rev. Biochem., 2016 85, 349-373.
2. Modi, S., et al. A DNA nanomachine that maps spatial and temporal pH changes in living cells. Nature Nanotechnology, 2009, 4, 325-330.
3. Modi, S., et al. Two DNA nanomachines map pH of intersecting endocytic pathways. Nature Nanotechnology, 2013, 8, 459-467.
4. Surana, S., et al. Designing DNA nanodevices for compatibility with the immune system of higher organisms. Nature Nanotechnology, 2015, 10, 741-747.
5. Saha, S., et al. A pH-insensitive DNA nanodevice quantifies chloride in organelles of living cells. Nature Nanotechnology, 2015, 10, 645-651.
6. Chakraborty, K., et al., High lumenal chloride in the lysosome is critical for lysosome function. eLife, 2017, 6, e28862.
7. Dan, K. et al., DNA nanodevices map enzymatic activity in vivo. 2018 (in revision).
8. Thekkan, S. et al A DNA-based fluorescent reporter maps HOCl dynamics in the maturing phagosome. 2018 (submitted)

Translesion DNA synthesis (TLS) overcomes arrest of replication forks at DNA lesions, by allowing synthesis across the damaged sites by specialized low-fidelity TLS DNA polymerases. This prevents double-strand breaks and genomic instability at the cost of increased point mutations. An siRNA screen performed in our lab in search for novel regulatory mammalian TLS genes, identified 17 novel TLS genes, one of which was PAPD7 (Poly (A) polymerase D7), a putative non-canonical poly(A) RNA polymerase. The biological role of PAPD7 is unknown yet.
We over-expressed and partially purified recombinant human PAPD7 and showed that it is indeed an adenylyltransferase. Measuring TLS across site-specific benzo[a]pyrene–G (BP-G), a major cigarette smoke DNA-adduct, we show that the down-regulation of PAPD7 decreased TLS across BP-G, and also decreased its mutagenicity. Further analysis showed that at least part of PAPD7 regulation of TLS is via its effect on monoubiquitination of PCNA (the DNA sliding clamp), a key step in TLS. RNA-seq analysis followed enrichment analysis showed that PAPD7 is involved in several biological functions including RNA metabolism, development, inflammation, signalling, cell cycle and DNA replication. Current studies are aimed at better understanding the molecular mechanism of TLS regulation by PAPD7.