Mycobacterium tuberculosis is an obligate human pathogen. However, our understanding of the MTB biology in humans is limited by the difficulty of accessing the sites of infection. Bacterial population genetics provides mechanistic insights into the biology of MTB in people. We have leveraged MTB population genetics to identify genes that are evolving to increase the bacterium’s ability to survive drug pressure. This analysis has revealed a novel regulatory circuit governing the integration of chromosomal replication and cell division. Genetic variation in the circuit components alters cell cycle and the ability to restart growth after antibiotic stress.
Past PMB Seminars
For a schedule of all Plant & Microbial Biology events, seminars, and lectures visit our calendar.
Transcriptional Governance: Mechanisms of Activation Control for the Auxin Response Factors
The Strader lab has been studying transcriptional output of the Auxin Response Factors, key regulators of plant growth and development, finding that protein condensation, nucleo-cytoplasmic partitioning, and activation domain activity can be modulated to integrate environmental and developmental cues into their transcriptional activity.
Most Delicious Poison: The Story of Nature’s Toxins–from Spices to Vices
I will discuss what motivated me to write a new book on the origin story of toxins made by plants and other organisms that humans use (and sometimes abuse) and I will give an overview of this general audience book.
Learning the grammar of plant regulatory DNA with MPRAs and long reads
Plant researchers have long sought to engineer endogenous gene regulation to improve crop traits, and to insert into crops multi-gene cassettes that encode metabolic pathways for bioproducts. However, we lack sufficient knowledge of the functional elements directing gene expression and the ways in which they interact – the regulatory grammar – to make the engineering of crop traits and pathways routine. Thus far, predicting the expression in plants of synthetic genes and pathways, even those composed of well-characterized DNA sequences, remains a major challenge. Indeed, when individual pathway genes are assembled into larger designs, their performance shows strong context-dependent properties. Moreover, our current tool set contains only a handful of regulatory elements, often of bacterial and viral origin, that constitutively and ubiquitously drive gene expression, contributing to expression interference, silencing and reduced crop fitness. Thus, new approaches are needed to engineer programmable and tunable gene expression. Our team has pioneered Plant STARR-seq, a reductionist but highly versatile MPRA, to test the activity of hundreds of thousands of regulatory elements in a dicot and a monocot system. The large scale of the resulting data allows for machine learning and in silico evolution of regulatory elements with desired features. I will discuss our recent efforts to understand insulators and silencers in plant genomes.
Genome-scale regulatory landscapes and long-range regulatory interactions are typically inferred from short-read data. To resolve the context-dependency of gene regulation, we need to move beyond averaging large numbers of small fragments that are mapped back to the genome; instead, we need to explore the regulatory events that occur simultaneously on single chromatin fibers. We have adapted Fiber-seq, a long-read single molecule method, for use in plants. Fiber-seq of maize leaf protoplasts faithfully recapitulates regulatory elements found in matched ATAC-seq samples and finds new elements. I will present results on regulatory activity in LTR retrotransposons, and show that Barbara McClintock’s discovery of transposon mobility may have been aided by less rigidly packed chromatin at these specific loci.
The PopZ Condensate: From Cytosol Organization in Bacteria to Synthetic Applications in Human Cells
Intracellular phase separation is increasingly recognized as a key organizer of biochemical processes within cells. PopZ, an intrinsically disordered protein, exemplifies this by forming condensates at the poles of Caulobacter crescentus, thereby directing the cell cycle's regulatory signals. This presentation will explore the mechanisms behind PopZ's condensation and its role in cytosolic organization. I will illustrate how the interplay of attractive and repulsive forces, governed by its helical oligomerization domain and a disordered region, precisely tunes the material properties of PopZ condensates. These properties are crucial for maintaining the integrity of cell division, thereby connecting molecular dynamics to the fitness of the organism. Lastly, I will demonstrate the potential application of these principles in designing modular, adjustable synthetic condensates for human cells.
Arnon Lecture: Photoprotection of photosynthesis through cyclic electron transport in chloroplasts
Cyclic electron transport around photosystem-I, and the associated cyclic photophosphorylation process in chloroplasts is enabled by two pathways, which depend on the PGR5 protein and the chloroplast NADH dehydrogenase-like complex, respectively. When both pathways are defective, photosynthesis and plant growth are significantly impaired. The pgr5 mutant of Arabidopsis is particularly sensitive to fluctuations in light intensity, which can lead to photodamage of photosystem-I. The lecture will discuss the molecular mechanism of the photoprotection of photosystem-I, afforded by this cyclic electron transport process.
Swarming motility and the control of flagellar number in Bacillus subtilis
Bacterial flagellar are complex transenvelope nanomachines, and both flagella number per cell and insertion pattern vary by species. For example, Bacillus subtilis assembles ~15 flagella per cell when swimming in liquid and we found that flagellar number must double in order to swarm across solid surfaces. I will discuss how a small protein SwrA controls flagellar number by inducing oligomerization of a two-component response regulator protein necessary for gene activation. I will also show that SwrA levels are restricted by a Lon/adaptor system that is antagonized when cells are in conditions that promote swarming. The talk will cover flagellar biology and behavior, fundamentals of gene activation, regulatory proteolysis, and the cell-surface contact response.
A weaponized phage suppresses bacterial competitors in wild populations of pathogenic bacteria
Bacteriophages, the viruses of bacteria, are proposed to drive bacterial population dynamics, yet direct evidence of their impact on natural populations is limited. Here we identified viral sequences in a metapopulation of wild plant-associated Pseudomonas spp. genomes. We discovered that the most abundant viral cluster does not encode an intact phage but instead encodes a tailocin - a phage-derived element that bacteria use to kill competitors for interbacterial warfare. Each pathogenic Pseudomonas sp. strain carries one of a few distinct tailocin variants, which target variable polysaccharides in the outer membrane of co-occurring pathogenic strains. Analysis of historic herbarium samples from the last 170 years revealed that the same tailocin and receptor variants have persisted in the Pseudomonas populations for at least two centuries, suggesting the continued use of a defined set of tailocin haplotypes and receptors. These results indicate that tailocin genetic diversity can be mined to develop targeted "tailocin cocktails" for microbial control.
In it together: Understanding and leveraging microbial symbioses to mitigate global change impacts
Coral reef ecosystems contribute ~$30 billion USD annually to the global economy and harbor 1/4 of all known marine species. However, human activities have driven the loss of 50% of the world’s reefs over the last 30 years, and 90% of remaining reefs are predicted to be threatened by 2030. Thus, there is an urgent need for human interventions to support reef resilience to warming seas, overharvesting and pollution. Various studies have documented the influence of microbial symbionts on host physiology, demonstrated that some hosts are relatively mutable in the symbionts they harbor, and shown that symbionts can shift under stress. The large population sizes and short generation times of microorganisms allow them to rapidly evolve traits such as heat tolerance. Furthermore, trophic interactions between corals and their predators may facilitate the dispersal of microbial symbionts to prospective hosts across reefs. Over the last five years, my research group has sought creative ways to leverage microbial symbionts (e.g., dinoflagellates in the family Symbiodiniaceae, bacteria, viruses) and trophic interactions to improve coral colony and reef health. This talk will describe these efforts and associated challenges, and identify areas where transdisciplinary collaborations may offer solutions.
Transcriptome homeostasis in Arabidopsis: nuclear-cytoplasmic cross-talk and RNA buffering
My lab investigates the roles of mRNA decay in shaping the Arabidopsis transcriptome. Measurements of mRNA decay rates has revealed both detailed information on the roles of some mRNA decay components and demonstrated wide-spread mRNA buffering (compensation for changes in mRNA half-life that maintains normal mRNA abundances). Roles of mRNA decay and buffering in a transcriptome response to stimulus will be discussed.