Keith Hengen

Assistant Professor of Biology
Washington University

Circuit-specific flickering of sleep & wake predicts natural behaviors: the minimal unit of brain sleep

Sleep and wake are understood to be slow, long-lasting processes that span the entire brain. The possibility that local circuits throughout the brain might routinely and independently switch between sleep and wake has been difficult to address due to reliance on surface measurements of brain rhythms to classify state.

By recording high resolution neural activity across diverse regions of the murine brain for 24 h, we learn reliable rules of sleep/wake embedding in each circuit at the scale of 100 microseconds and 100 microns, a 7 order of magnitude improvement in resolution over standard approaches.

We show that diverse microcircuits regularly switch between sleep-like and wake-like states (flickers), independent of the rest of the brain and the arousal state of the animal. Furthermore, high sleep pressure suppresses wake flickers within sleep, but does not modulate sleep flickers during wake. In contrast, sleep flickers during complex, natural behavior results in a momentary pause of movement.

Our results reveal that sleep and wake arise from an unstable patchwork of states throughout the brain.

THURSDAY  I  DEC. 8 I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Katherine Davis

Assistant Professor of Chemistry, Physics graduate Program member
Emory College

Structural insights into the biosynthesis and bioactivity of natural products

Natural products provide a powerful foundation from which to develop novel therapeutics. Despite their utility, our understanding of both their biosynthesis and mechanisms of action are often incomplete, due in part to the scarcity of structural data depicting their interactions with associated bio-synthetic enzymes and/or targets.

Ribosomally synthesized and post-translationally modified peptides (RiPPs), for example, are a diverse class of bioactive peptides whose simple biosynthetic pathways make them attractive for bio-engineering efforts. However, the structural basis for substrate recognition and recruitment by their respective tailoring enzymes remains unclear. Hydroxyalkylquinolines (HAQs), by contrast, have been studied extensively for their marked antimicrobial activity, yet insights into the origin of this activity are limited.

In this talk, I will present X-ray crystallographic data and computational modeling studies that elucidate the structure and dynamics of associated enzyme-ligand interactions. In particu-
lar, our results provide new insights into the role of a putative substrate-
binding domain associated with RiPP-biosynthesis via study of the radical S-adenosylmethionine (SAM) enzyme, SuiB, and confirm the hypothesis that competition with the co-substrate ubiquinone is the basis for dihydroorotate dehydrogenase inhibition by bacterial HAQs.

THURSDAY  I  NOV. 10  I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Fixen Lab

University of Minnesota

A ‘Fix’-ing to understand electron flow in a purple nonsulfur bacterium

Bacteria are promising biocatalysts for the production of biofuels and bioproducts because they can tap into sources of energy that we are still struggling to use (e.g. plant biomass, sunlight, and waste streams), and the ATP and electrons generated from metabolizing these sources can power metabolic pathways that produce energy-rich
compounds.

Anaerobic bacteria and archaea, in particular, have evolved diverse ways of managing electron flow to pathways that often naturally result in the release of compounds like butanol, ethanol, methane, hydrogen, etc. Understanding mechanisms that control electron flow is necessary to get these organisms to produce more of these com-
pounds.

In the Fixen lab, we are working to understand electron flow in the anoxygenic phototroph, Rhodopseudomonas palustris, by:

1.characterizing components of electron transfer and factors that determine their interactions;

2.) understanding how these components are regulated by environmental factors; and

3.) identifying and characterizing new pathways that can use these electrons to make valuable compounds.

By understanding how R. palustris controls electron flow, we hope to find new ways to divert more electrons down pathways that generate energy-rich compounds.

THURSDAY  I  OCT. 27  I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Harcombe Lab

Associate Professor, Ecology, Evolution and Behavior
University of Minnesota

A metabolic approach to microbial community robustness

As we strive to manage critical microbial communities we must understand how these systems respond to perturbation. We use a combination of metabolic modeling and laboratory co-cultures to investigate how the physiology of cells determines the content, function and dynamics of microbial communities.

We have found that cross-feeding tends to stabilize species ratios, but makes community growth less robust to perturbations. We specifically investigate the impact of antibiotics, bacteriophage and mutations in a system in which Escherichia coli and Salmonella enterica rely on each other for essential metabolites.

Our work suggests that metabolic interactions between species can have predictable impacts on both ecological and evolutionary responses to perturbation in microbial communities.

THURSDAY  I  OCT. 20 I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Yujie Men

Assistant Professor, Chemical and Environmental Engineering
University of Minnesota

Multi-Omics Investigation of Carbon Flux Networks in Environmental Bacteria of Biotechnological Relevance

Carbon-fluorine (C–F) bond is the strongest single bond in nature. Per- and polyfluoroalkyl substances (PFAS) are a large group of man-made chemicals with broad applications causing severe environmental concerns due to their persistence and toxicity.

Although microbial defluorination of naturally occurring and less fluorinated compounds, such as monofluoroacetate, has been well studied, biodefluorination pathways and mechanisms of highly fluorinated PFAS have not been clearly understood.

An introduction of the current research status of microbial defluorination will be
given first, followed by the most recent findings on microbial defluorination of a variety of per- and polyfluorinated compounds, defluorination pathway elucidation, and the identification of responsible microorganisms.

THURSDAY  I  OCT. 13 I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Adamala Lab

Assistant Professor, Genetics, Cell Biology, and Development
University of Minnesota

Life but not alive: bioengineering with synthetic cells

All of biological research is done on a single sample: that of modern, terrestrial life. In the quest to engineer synthetic living systems, we seek to expand that sample size, enabling investigation to general properties of life in the lineage agnostic, synthetic organisms.

Synthetic minimal cells are liposomal bioreactors that have some, but not all properties of live cells. Creating artificial living systems allows us to diversify the chassis of biological studies, and provides new opportunities for bioengineering.

We can answer questions about healthy and diseased natural cells, and ask new questions about the limits and possibilities of biology.

THURSDAY  I  OCT. 6 I  3:30-4:30 PM CST  I  HYBRID SEMINAR