We are going virtual! Please mark your calendars and get in touch if you want to present your work. The format is flexible but will typically be 20-30 min seminar followed by 20-30 min Q&A/discussion. 

We are looking forward to it! 

Joseph Quagraine
Masters Candidate, Regan Lab
Queen's University

Anthropogenic activities have led to widespread heavy metal contaminants such cadmium and arsenic. When left untreated, they pose risk to both human and ecosystem health as well as further reduce arable lands. Phytoremediation, which is the use of plants and their associated microorganisms to clean up such contaminants, is environmentally friendly, cost effective and fast-growing trees such as Populus sp. are good candidates for phytoremediation because of their tolerance of heavy metals, high biomass and their distribution across much of the northern hemisphere. However, the molecular mechanisms underlying poplar’s phytoremediation are poorly understood. Although Populus is a model tree species, with a sequenced genome and many genetic and genomic resources, the identification of genes for important tree traits is still slower than in other model plants such as Arabidopsis. This study uses a functional genomics approach to identify genes related to bioremediation by taking advantage of a large collection of activation tagged poplars (Populus tremula x P. alba hybrid 717-1B4) created by Dr. Sharon Regan’s  Lab. After screening over 1700 independent transgenic lines for characteristics that could affect phytoremediation, seven mutants had altered root biomass whereas 15 mutants had altered response to heavy metals. Of the seven root phenotypes identified, two previously studied mutants, called rippled leaf and adventitious root were further investigated. RT-qPCR analysis showed an up-regulation of CYCLIND1;2 and E3 ubiquitin-protein ligase XBAT32/33 in the roots of rippled leaf and adventitious root mutants respectively. The upregulation of CYCLIND1;2 is suspected to increase root biomass through accelerated cell cycle division. XBAT32/33 on the other hand is suspected to promote the production of lateral roots through the regulation of ethylene biosynthesis. Altogether, this study provides a starting point in the quest to discover key genes responsible for phytoremediation and could lead ultimately to the development of biomarkers for selection of superior trees from natural population for clean-up purposes.

Dr. Matthew Andrusiak
Biological Sciences, University of California, San Diego

The genetic mutation and de-regulation of prion-like domain (PrLD) containing proteins is over-represented in human disease. Despite their role in human disease, little is known about how PrLD’s regulate protein function. PrLD-containing proteins are often capable of liquid-liquid phase separation (LLPS) resulting in the formation of non-membrane bound cellular compartments. The in vivo function and cellular mechanisms regulated by LLPS remain unknown. My work identified the PrLD coding gene tiar-2, a C. elegans member of the TIA1 family, as an intrinsic inhibitor of axon regeneration. TIAR-2 forms granules and inhibits axon regeneration in a dose-dependent manner. TIAR-2 undergoes LLPS in vitro and granules have liquid-features in vivo. Following axon injury, TIAR-2 granule number increases, and their liquid-like features are significantly reduced. Importantly, the PrLD of TIAR-2 is necessary and sufficient for its ability to inhibit regeneration and form granules. Post-translational modifications, such as phosphorylation, have been shown to act as molecular switches regulating LLPS. TIAR-2 is serine phosphorylated and this modification is required for TIAR-2 granule formation and function in axon regeneration. This work identified axonal injury as an acute cue that modulates the formation of LLPS granules and the function of the PrLD containing protein TIAR-2. Future research efforts will focus on understanding the role of prion-like domains in the regulation of biological outputs during nervous system and organismal development, as well as following neuronal injury.

Transcription is essential for life and in eukaryotes it is performed by one of several RNA polymerases (RNAP). Of these, RNAPII is responsible for the synthesis of all mRNAs and many non-coding transcripts, an activity that requires the integration of general and gene-specific signals. However, how these activities are coordinated and contribute to the response to environmental contexts remains poorly understood, despite a clear significance in the adaptation, health and survival of all organisms. Furthermore, the extent to which genetic variability affects transcription and thus modulates individual differences in the response to challenge remains largely unknown. Using yeast, I have identified new players in the response to oxidative stress, a challenge that affects all organisms and that can have grave consequences for cellular integrity. I also showed that the transcriptional response to oxidant involved alterations in both mRNA synthesis and mRNA decay, effects that must be teased apart in order to fully understand how organisms respond to environmental contexts. Furthermore, my work in fruit flies identified sex-specific differences in gene expression under normal and stress conditions, thus underscoring the importance of considering sex when studying the molecular underpinnings of the biological embedding of experience.

Over the last thirty years, several molecular events operating on the products of the central dogma processes of DNA replication, transcription and translation have been found to play an important role in controlling gene regulation in a rapid and adaptive manner in response to various external stimuli. Here, I will present unpublished work investigating the role of three such “post-genetic” phenomena: extrachromosomal circular DNA (eccDNA) production, RNA splicing, and protein phosphorylation in the model plant Arabidopsis thaliana. First, I will discuss on-going work studying the role of eccDNA molecules in plant responses to heat-stress through the invention of a new DNA sequencing method called CIDER-Seq. CIDER-Seq leverages the power of long-read PacBio sequencing technology to produce accurate sequences of eccDNA (and other circular DNA such as viruses) without computational sequence assembly. Using CIDER-Seq we have generated the first comprehensive sequence dataset of eccDNA in plants, gaining insights into eccDNA composition and function that have implications in stress and evolutionary biology. I will also discuss recent work using quantitative proteomics and phosphoproteomics that has uncovered new regulatory roles for protein phosphorylation during phosphate starvation. Collectively, these proteomics and genomics-technology driven experiments point towards an important role for genome plasticity and post-genetic regulation in plant responses to future challenges in agriculture such as rising temperatures and declining nutrient supply. Next I will describe future projects employing genomics, proteomics, genome editing, and chemical genetics approaches to investigate eccDNA and RNA splicing regulation in plants. Finally, I will briefly touch upon my work outside the lab: in science communication, research culture, and equity in science publishing with the premier open-access life science journal eLife. 

Muscles are made up of muscle fibers, each containing thousands of cylindrical segments called sarcomeres, which are the smallest contractile unit of muscles. When animals move, proteins in the sarcomere move past each other, shortening the muscles. In the relaxed state, all sarcomeres have the same length and diameter. To study muscle biology I use the fruit fly Drosophila. Their flight muscles are extremely regular, because they have to mediate 200 small contractions per second, and are therefore ideally suited to detect phenotypic variations. Sarcomeres are composed of antiparallel actin and myosin filaments that slide past each other. Both filaments are anchored to big protein complexes that provide structural stability. The Z-discs anchor actin filaments and the M-lines myosin filaments. This fascinating structural arrangement provides the basis of muscle contraction. The general sarcomere structure is well known but the mechanisms that assemble sarcomeres from unorganized components and maintain sarcomeres during muscle contractions are not well understood. The Z-disc anchors actin filaments and thus coordinates sarcomere assembly and function. Accordingly, most mutations linked to myopathies are components of the Z-disc.

To study sarcomere assembly and function, I combine the power of Drosophila genetics with quantitative microscopy and a novel bioinformatics method for inferring protein-protein interactions.  First, I will talk about how the scaffolding protein Zasp mediates sarcomere growth through a finely tuned protein oligomerization mechanism. Oligomerization is induced by long Zasp isoforms and terminated upon upregulation of shorter Zasp isoforms, which lack multivalent LIM domains. The balance between these two isoforms sets the stereotyped size of sarcomeres. Second, I will describe how elastic proteins help maintain sarcomere stability during muscle contraction. In this model, two elastic proteins filamin and titin function together as an elastic bridge between thin filaments of opposing sarcomeres. Both filamin and titin have protein regions than unfold upon pulling forces and then refold, essentially working as springs. Their function is required for compensating for the contractile forces and maintaining the sarcomere structure. Finally, I will discuss future directions and approaches.

Bethany Holland
Long Lab
University of Illinois

The allocation of resources to roots and shoots can greatly alter total plant mass. Allocation is thought to be a consequence of growth processes (i.e. uptake rates, transport rates,  growth rates) and the communication between them via signaling mechanisms. Changes in the environment create imbalances in carbon and nitrogen concentrations in the plant. These imbalances induce internal feedbacks that alter key growth processes but how they function together to define allocation remains unclear. Here, the mechanisms responsible for allocation are investigated by creating a model of carbon sensitive and nitrogen sensitive feedbacks on growth processes. The extent to which the model responds to changes in carbon and nitrogen availability is evaluated by simulating a combination of two atmospheric CO2 and two soil nitrogen treatments along with an additional test of defoliation on leaf mass. Overall this shows that a combination of known signalling mechanisms are sufficient to reproduce experimentally observed responses to external resource availability.

Chantelle J. Capicciotti
Department of Chemistry, Department of Biomedical and
Molecular Sciences, Department of Surgery
 Queen’s University

The thick “sugar coating” that covers all of our cells plays important roles in biology and disease. For instance, the complex carbohydrate structures found in this coating, called glycans, change to abnormal states in diseases like cancer. However, understanding how glycans affect biological processes and how we can target these molecules for therapies has been difficult. As a result, novel chemical biology tools are needed to meet the demand for new information and advance our understanding of the function of these important biomolecules. In this talk, I will describe the interdisciplinary approaches the Capicciotti Group is employing to tackle the challenge of studying glycan function in cells. Using chemical and biochemical strategies, we are examining the roles of precise complex glycan structures in immunological and inflammatory responses, and how specific glycan-protein interactions influence cancer immunoevasion. Approaches for imaging cancer-associated glycans and identifying novel glycan biomarkers as therapeutics targets to facilitate the development of glycan-based strategies for combatting disease will also be discussed.

Akos Nyerges
Postdoctoral Researcher (Church Lab)
Harvard Medical School

Akos is interested in advancing genome editing to accelerate evolutionary processes and thus support synthetic genomics and drug development. To this aim, he has so far developed tools to perform precise genome engineering in human pathogenic bacteria and hosts for microbial fermentation. His PhD project focused on the accelerated prediction of antibiotic resistance and the exploitation of resistance mechanisms for more-effective therapeutic solutions.  In the course of his postdoctoral research, he is now applying accelerated laboratory evolution to understand the design-principles of functional genomes.

Akos’ talk will summarize how bacterial synthetic biology opened new opportunities in evolutionary biology, synthetic genomics, and drug development. He will describe how they expanded the toolset of genome engineering and directed evolution to some of the most concerning pathogenic bacteria, and how they later used these advances to forecast resistance processes for antibiotics.

Akos will introduce these developments through his latest project that led to the prediction of potential resistance processes against an antibiotic that is right now in clinical trials and allowed the rapid analysis of resistance mechanisms for novel drugs (i.e., https://doi.org/10.1073/pnas.1801646115 and https://doi.org/10.1101/495630).

Dr. Scott Farrow
Director of Biological Discoveries,
Noblegen, Inc.

The use of natural products by humans’ pre-dates written history, and while synthetic organic chemistry has produced new commercially relevant compounds, the organisms found in nature are the master chemists.  These organisms have evolved an inexhaustible array of natural product scaffolds that are used directly in medicine (i.e. morphine from opium poppy), exploited for drug development (i.e. salicylic acid for acetylsalicylic acid or Aspirin), and used across industries including but not limited to food (i.e. health products such as green foods), cosmetic (i.e. scents in perfumes) and fuel (biofuel, specialty fuels).  While the utilization of natural products has helped address the needs of a growing human population, challenges remain that threaten our well-being.  In this context, nature remains a rich source of solutions to these challenges.  For example, the utility of natural products as the source for food and medicine is still significant.  In this seminar I will discuss my work on the elucidation of several key medicinal plant biochemical pathways (morphine, vinblastine and ibogaine) and outline traditional and modern approaches for accessing known and novel high-value natural products.  I will also discuss my new role as director of biological discovery at Noblegen and some of the work we are conducting to access sustainable foods and medicines.