Tracy M. Sonneborn Lecture Series

For more than a century, research on genetic regulation has predominantly focused on genes. In this presentation, I will introduce a whole-genome paradigm of genetic regulation that extends beyond genes to encompass all major genetic constituents within the genome. This novel regulatory framework is mediated by tens of thousands of small non-coding RNAs known as Piwi-interacting RNAs (piRNAs) and their associated Piwi proteins, a subfamily of the small-RNA binding Argonaute (Ago) protein family discovered by my lab in 1998. PiRNAs typically range from 24 to 32 nucleotides in length and correspond to diverse genomic sequences. Our recent investigations indicate that the Piwi-piRNA pathway orchestrates the expression of protein-coding genes, transposons, pseudogenes, long noncoding RNAs (lncRNAs), and governs the functions of centromeres and telomeres at epigenetic and post-transcriptional levels. This holistic regulation across the entire genome is crucial for determining germline fate and sustaining stem cell self-renewal.

Germline is the sole cell type that is capable of transmitting genetic information to the next generation, supporting the continuation of metazoan life in the last 1.5 billion years. In the face of somatic cells’ limited replicative life span, the germline’s ability to continue and sustain for infinite period of time is remarkable. In this lecture, I will discuss how germline maintains their genome through generations, and how this process may be intertwined with the process of genome evolution, leading to eventual splitting of lineages, i.e. speciation. Specifically, the topic includes our recent findings on asymmetric division of germline stem cells and meiotic cells contributes to germline immortality and genome evolution.

Helical cell shape is necessary for efficient stomach colonization by Helicobacter pylori, the first bacteria to be designated as a class I carcinogen by the World Health Organization. Through genetic screens and biochemical assays, we have identified peptidoglycan (PG) cell wall modifying enzymes (Csd1, Csd3/HdpA, Csd4, Csd6, Slt) and non-enzymatic proteins (Csd2, Csd5, Csd7, CcmA, MurF) that collaborate to promote helical cell shape. Additionally, super-resolution microscopy has revealed that the helical centerline pitch and radius of wild-type H. pylori cells dictate sidewall cell surface curvatures of considerably higher positive and negative Gaussian curvatures than those present in straight- or curved-rod bacteria. I will discuss recent work utilizing subcellular localization of cell shape determining proteins and PG features to elucidate the mechanisms by which H. pylori promotes and maintains helical cell shape as well as our efforts to understand the host selective forces favoring helical cell shape.

Cells of diverse organisms, from cyanobacteria to humans, execute daily physiological programs that are driven by circadian oscillators. The circadian clock of the cyanobacterium Synechococcus elongatus regulates global patterns of gene expression, metabolism, and the uptake of exogenous DNA. We use S. elongatus as a model to understand how a cell keeps track of time, executes activities according to a temporal program, and synchronizes the internal clock with the external solar cycle. An extraordinary feature of the cyanobacterial circadian oscillator is that its 24-h timing program can be reconstituted in vitro based on the proteins KaiA, KaiB, and KaiC, and this in vitro oscillator recapitulates the properties observed in vivo. Real-time monitoring of the interactions among clock components during the cycle allows structural, biochemical, and biophysical analyses of the association of components of the oscillator with one another and with their interacting partners that have been characterized in vivo. We can now trace temporal output from the oscillator, via signal transduction kinases, to a master circadian transcription factor, and reconstitute the rhythmic binding of the transcription factor to clock-regulated promoters. Genetic, genomic, and metabolomic approaches link the circadian transcriptome to the diurnal physiology and metabolism of the cyanobacterium’s daily life.

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With precision, thoroughness, and infectious enthusiasm, Tracy Sonneborn also contributed unstintingly to teaching at Indiana University. In spite of the many attempts to entice him away, he remained loyal to IU, finding here the environment he thought was best. To honor his contributions to science and his outstanding career Tracy Sonneborn’s friends and colleagues initiated the Sonneborn Lectureship in 1981.

“Whatever the final outcome of studies of these phenomena, he must take his place among the most brilliant and devoted experimentalists in the history of biology and a true giant, like no other, in the field of protozoan research.” John Preer