Integrated Calendar

Recent droughts and floods in California have drawn attention to the vulnerability of our water-supply system to present and future climate variability. A recent analysis of climate-model simulations suggests that wet and dry conditions in California may be predictably linked to tropical and high-latitude conditions, a hypothesis that should be testable using paleoclimate records. Abundant paleoclimate evidence indicates that natural whiplash between wet and dry conditions characterized California’s climate throughout the last 4000 years, especially during the Medieval Climate Anomaly (~AD 950 to 1250), but the chronologies of the records are not precise enough to correlate to tropical and high-latitude records in order to test the model prediction. Our recent work at Mono Lake, a climatically sensitive lake on the arid eastern side of the Sierra Nevada mountain range, has focused on exploring and developing radiocarbon dating of pollen purified by flow cytometry as a tool for high-resolution dating of lake records. Our results suggest that pollen can be reliably separated and dated, but (like everything in lakes) must be interpreted within the specific geologic system where it was produced, deposited, and preserved. If pollen dating proves robust in many lake systems, it may provide the high-precision chronologies required for spatial mapping of past terrestrial climate changes.

I will tell you two stories of adaptation of populations aided and enriched by statistical physics approaches.

The first story is about the adaptation of bacteria with CRISPR. CRISPR-Cas is a famous biology buzz word, due to its applications to gene editing. However, CRISPR-Cas is also a prokaryote immune system. It works as a “library” of previous infections. This library contains snippets of exogenous genetic material. With a new infection, the library is consulted, and if a match is found, the attempt will be made to neutralize the intruding genome. Bacteria use CRISPR-Cas as an immune system against phages and plasmids. Such immunity is hereditary and dynamic — it can be gained and lost during the lifetime of the single bacteria. Also, the process of acquiring snippets when exposed to the same phage is stochastic, and the same strain bacteria in a population contain different CRISPR loci content and thus variable immunity to the phage. We use dynamical systems approaches to predict the shape of this diverse distribution of CRISPR loci content within a bacterial population as a function of two crucial parameters — the rate of acquisition and the immunity to the phage.

The second story is about adaptation on a rugged fitness landscape. A crude measure of adaption to a new environment called fitness. Often one defines fitness as the expected growth rate. The higher the fitness, the more thriving is a population. What happens over long times for a population with a finite genome — when all beneficial, fitness mutations, are exhausted? Contrary to expectations, the experiments show that fitness does not reach a plateau. Here we introduce a spin-glass microscopic model, where a genome can be represented as a spin configuration, and individual spins are genes. The fitness plays the role of minus the Hamiltonian of the system. We use numerical approaches and estimates to study hopping between metastable states on a rugged fitness landscape. We show that with gene interactions (interacting spins), double beneficial mutations (flipping of pairs of spins) can lead to a slow, logarithmic increase of fitness in a wide class of cases.

Malaria, caused by Plasmodium falciparum (Pf), is a devastating parasitic disease affecting hundreds of millions of people worldwide. Many pathogens use Extracellular Vesicles (EVs), to manipulate their hosts by diverting host signaling pathways to facilitate infection. In this study, we investigated the role of EVs secreted from Pf-infected red blood cells (RBCs) in altering their residing host. Using AFM-based assay, we found that the parasitic EVs significantly modify the host membrane and make it softer. Importantly, we demonstrate that the cytoskeletal structure of the RBC is being disrupted upon treatment with these EVs. Remarkably, by proteomic analysis we identified the 20S proteasome in Pf-derived EVs and further verified this complex is active within the parasitic-EVs. We further demonstrated the involvement of the 20S proteasome in host cytoskeleton degradation. This cytoskeleton degradation by the 20S proteasome leads to “priming” of naive RBC (uRBC) and thus to elevated parasitemia levels. Our results demonstrate, for the first time, that Pf-derived EVs alter both mechanical and molecular properties of their immediate host, the RBCs, by delivering active 20S proteasome and for the benefit of the parasite.

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. Building on a prolonged examination of hydrogen-bonded frameworks and inclusion compounds derived from guanidinium organosulfonates, we have devised an approach to molecular structure determination that relies on a versatile toolkit of these host frameworks, which form crystalline inclusion compounds with target guest molecules in a single-step crystallization. This approach complements the so-called crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework, while circumventing many of its challenges. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination. This presentation will describe examples of this approach to structure determination, preceded by an account of the unusual properties and resilience of these hydrogen-bonded frameworks, their substantial diversity of framework architectures, and their utility in other applications.