Eric Sembrat's Test Bonanza

Diffusion of single molecules and organelles in living cells has attracted considerable interest. The motion so essential for intra- and intercellular transport, regulation, and signaling, and hence for the life within cells exhibits surprising deviations from normal Brownian motion. Using optical tweezers combined with single particle tracking inside living cellular organisms we study intracellular diffusion of nano-sized organelles inside living cells. The temperature increase caused by absorption by the laser light as well as the potential physiological damage are important also to consider and will be addressed [1,2]. Lipid granules inside living S. pombe yeast cells perform anomalous diffusion, with subdiffusion being most predominant at short time-lags, and the biological functions giving motility footprints at longer time-lags [3]. At very short timescales, the subdiffusion of lipid granules is well described by the laws of continuous time random walk theory and at longer timescales the granule motion is consistent with fractional Brownian motion. Ordinary Brownian diffusion exhibits ergodicity: long time averages of a measured process for a single particle are equal to the corresponding average over a statistical ensemble. Ergodicity is also fulfilled for anomalous processes governed by fractional Brownian motion. In our analysis of the passive diffusion of liquid granules in living fission yeast cells and in endothelial cells we demonstrate that the diffusion is not only anomalous, but that ergodicity is indeed violated on biochemically relevant time scales [4,5]. Ergodicity breaking implies that time averages based on individual trajectories are random variables, such that our common wisdom associated with the picture of Brownian motion fails. While ergodicity breaking is expected in large live organisms it is surprising to find it already for a small particle essentially coupled to a thermal heat bath thus indicating that basic concepts of statistical Physics must be replaced when we analyze certain aspects of biomolecular dynamics in the cell.

1. A. Kyrsting, P.M. Bendix, D.G. Stamou, and L.B. Oddershede, Nano Letters, vol 11 p.888-892 (2011).
2. M.B. Rasmussen, L.B. Oddershede, H. Siegumfeldt, Applied and Environmental Microbiology, vol.74, no.8 (2008).
3. I.M. Tolic-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, PRL, vol.93, p.078102 (2004).
4. J.H. Jeon, V. Tejedor, S. Burov, E. Barkai, C. Selhuber, K. Berg-Sørensen, L. Oddershede, R. Metzler, PRL, vol. 106 p.048103 (2011).
5. N. Leijnse, J.-H. Jeon, S. Loft, R. Metzler, L.B. Oddershede, EPJ accepted (2012).

Most predictions for binary compact object formation are normalized to the present-day Milky Way population. In this talk, I suggest the merger rate of black hole binaries could be exceptionally sensitive to the ill-constrained fraction of low-metallicity star formation that ever occurred on our past light cone. I discuss whether and how observations might distinguish binary evolution uncertainties from this strong trend, both in the near future with well-identified electromagnetic counterparts and in the more distant future via third-generation gravitational wave detectors.

Trapped attractive atomic Bose-Einstein condensates (BECs) in three spatial dimensions are known to exist for some finite time only. This is because the gas is prone to self-collapse, due to the attractive nature of the interaction. The 'mainstream' way to describe the state of the condensate is a mean-field (MF) theory, that assumes total condensation of the system.  In this talk I will introduce the notion of fragmentation, in contrast to coherence, and show that the states of definite angular momentum of the 3D many-body system cannot be condensed MF states. With this at hand, I examine the impact of the angular momentum to the stability of the attractive gas and show that there is a general stabilizing tendency.

Squeezed states allow interferometers to surpass the standard quantum limit of the Heisenberg uncertainty principle.  Here we study spin-nematic squeezing of a spin-1 condensate following a quench through a nematic-ferromagnetic quantum phase transition.  We observe up to -8.3 dB squeezing in the variance of the spin-nematic quadratures.  This squeezing is observed for negligible occupation of the squeezed modes and is analogous to optical two-mode vacuum squeezing [1].

1. C.D. Hamley, C.D. Gerving, T.M. Hoang, E.M. Bookjans, and M.S. Chapman, “Spin-Nematic Squeezed Vacuum in a Quantum Gas,” To appear in Nature Phys.

 Cosmological hydrodynamical simulations are a useful tool for following the formation and evolution of galaxies over long timescales, but we must prescribe accurate models for the physics on small scales, below the resolution limits of our simulations. I investigate several different "subgrid models" at these scales to see what their effects are on a single Milky Way sized galaxy evolved from just after the Big Bang until the present. I grade the success of each model on how well it matches the dynamics of typical disk galaxies, creates a realistic star formation history, and produces a reasonable circumgalactic halo.

Membrane proteins are critical components of all cells, controlling, e.g., signaling, nutrient exchange, and energy production, and are the target of over half of all drugs currently in production.  At an early stage of their synthesis, nearly all membrane proteins are directed to a protein-conducting channel, the SecY/Sec61 complex, which permits access to the membrane via its lateral gate.  By combining molecular dynamics simulations with cryo-electron microscopy data, we recently resolved the first structure of a membrane-protein-insertion intermediate state of SecY bound to a translating ribosome, with a transmembrane (TM) segment caught at the open gate. Beginning from that state, multi-microsecond simulations of different putative TM segments at the gate have been carried out. The simulations reveal spontaneous motion of the TM segment, either inserting into the membrane or toward the channel interior, depending on its sequence, in agreement with a thermodynamic partitioning proposed previously.  However, attempts to quantify this partitioning led to experiment- and simulation-based scales for the free-energy insertion cost of various amino acids that differ significantly, leaving open the question of the true insertion process.  Now, using novel free-energy calculations and by carefully matching the context of the simulations to experiment, I will demonstrate a significantly improved agreement for multiple membrane-protein-insertion assays.  Thus, it is suggested that the discrimination step between membrane-inserted and secreted states of a nascent protein occurs primarily in the SecY channel.

In the natural world, complex behaviors such as learning, aggression and sleep are regulated by interconnected networks of genes and their products. Owing to their nontrivial topology and large number of components, most of these networks are poorly understood and consequently, our knowledge of how diverse behaviors arise remains limited. In this talk, I will argue that the fruit fly circadian clock, a genetic circuit that signals to and modulates several key behavioral networks, is an ideal system with which to dissect the fundamental principles that govern organismal behavior. I will discuss recent results from experimental studies at the transcriptional and post-translational levels of the fly clock as well as simple mathematical models aimed at understanding fruit fly locomotion. The talk will end with an outline of future studies using the fly that will provide novel mechanistic insights into how complex behavior emerges from simple molecular events. 

Engineered biological circuits expressed in living cells are becoming increasingly attractive as a technology, with applications ranging from biofuel production to medical treatments.  A major goal in synthetic biology is to facilitate the rational design of biological circuits by discovering design principles.  In this talk, a brief background to synthetic biology will precede a discussion of three topics (synthetic oscillators, queueing systems, and multicellular environments) where such design principles have been explored by us.

Riboswitches are RNA elements located in the untranslated regions of mRNAs that regulate gene expression by sensing and binding target cellular metabolites. In bacteria, they bind specific metabolites with a conserved aptamer domain, resulting in a change of the folding patterns of downstream expression platform that controls transcription termination or translation initiation. Purine riboswitches, which are among the simplest, display remarkable ligand selectivity and carry out entirely different functions despite the structural similarity of the aptamers. In this talk I will describe coarse-grained to map the folding landscape of purine riboswitches.  The folding landscapes provide insights into the differences between two purine riboswitches.  The results of the simulations are used as guide to develop a kinetic network model at the system level.