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Interest in RNA dysfunction in ALS recently aroused upon discovering causative mutations in RNA-binding protein genes. Focusing on the causes and consequences of miRNA dysregulation in amyotrophic lateral sclerosis (ALS) we will understand how advances in sequencing and molecular technologies enable deciphering the contribution of noncoding RNAs to Neurodegeneration. In the past, we identified extensive down-regulation of miRNA levels is a common molecular denominator for multiple forms of human ALS. We further demonstrated that pathogenic ALS-causing mutations are sufficient to inhibit miRNA biogenesis at the Dicing step. These works position miRNAs downstream of the initiating mutations that drive ALS and encourage testing what are the specific miRNAs that play roles in motor neurons and whether mutations in miRNA genes will be able to causatively initiate the disease.

We observe spontaneous Hawking radiation, stimulated by quantum vacuum fluctuations, emanating from an analogue black hole in an atomic Bose-Einstein condensate. The Hawking radiation is observed via the correlations between the Hawking radiation exiting the black hole and the partner particles falling into the black hole. The quantum nature of the Hawking radiation is observed through entanglement, by comparing the Fourier transform of the corre-lations to a measurement of the population. This comparison shows that the experiment is well within the quantum regime, since the measured Hawking temperature determined from the population distribution is far below the upper limit for quantum entanglement. A broad energy spectrum of entangled Hawking pairs are observed. Maximal entanglement is ob-served for the high energy part of the Hawking spectrum, while the lowest energies are not entangled. Thermal behavior is seen at very low energies where the finite extent of the corre-lation function implies frequency dependence. Thermal behavior is also seen at high energies through the agreement of the correlation spectrum with the appropriate function of the Planck distribution. Further insight is obtained by a preliminary experiment in which the horizon is caused to oscillate at a fixed frequency, which stimulates waves travelling into and out of the black hole. The rate of particle production by the oscillating horizon is consistent with the measured Hawking temperature. Furthermore, the observed ratio of the phase velocities of the Hawking and partner particles are consistent with this preliminary ex-periment, as is the width of the Hawking/partner correlation feature. Additional confirmation of the results is obtained through a numerical simulation, which demonstrates that the Hawk-ing radiation occurs in an approximately stationary background. It also confirms the width of the Hawking/partner correlation feature. The measurement reported here verifies Hawking’s calculation, which is viewed as a milestone in the quest for quantum gravity. The observation of Hawking radiation and its entanglement verifies important elements in the discussion of information loss in a real black hole.

Microbial communities are ubiquitous – found in natural and anthropogenic environments – and regulate processes spanning vast scales and ecological niches from the human microbiome to biogeochemical cycles. Surface-associated bacterial communities, called biofilms, are smart materials: they are self-organizing, self-renewing, respond to environmental stimuli, and perform complex functions. Therefore, biofilms represent an ideal system in which to study structure-function relationships in bacterial communities. Chemical gradients, such as of oxygen, nutrients, and signaling molecules, determine critical processes within biofilms. Biofilm morphology, species segregation and organization affect these gradients and thus community function. In this talk, I will describe our efforts to parse and manipulate the interactions governing community development in multispecies bacterial biofilms of Escherichia coli and Pseudomonas aeruginosa. These species have an antagonistic relationship in coculture, and we have identified some of the chemical and biophysical driving forces of these interactions, including a new biofilm dispersal signaling pathway. Furthermore, using microfabricated growth substrates, we are able to modulated the competitive signaling interactions within these coculture biofilms. Structured substrates alter biofilm morphology and deterministically switch a biological signaling pathway between E. coli and P. aeruginosa via manipulation of metabolite exchange rates. In this way, physical cues are transduced to chemical stimuli which control biofilm outcomes and community properties, including antibiotic susceptibility and probiotic resistance to pathogens. With these and other studies of biophysical mechanisms of bacterial signal transduction, we are developing design principles for engineering the structure and properties of multi-species bacterial biofilms.