Invited Speakers 2017

Here is the list of the speakers that have accepted our invitation to speak at this year's symposium, with a link to their research page. We will update this page periodically when the invitees confirm their attendance.

Xavier Belvaux | Monsanto Company, Saint Louis, USA

Natural tolerance and resistance to glyphosate

The Monsanto company has a long history of spearheading research, development and commercialization of agricultural innovations. We look back to understand which innovations and creativity were instrumental for Monsanto to grow to the company that it became today and the related transformations that Monsanto needed to implement and allowing to drive these innovations to the market place. We will describe the vision of where, why and how the company projects its future agricultural role. This part will touch upon enabling sciences and innovation priorities within the major technology platforms (crop protection, plant breeding, plant biotechnology, data science and agricultural biologicals) with the intend to deliver integrated agricultural solutions. Impacting discoveries tend to create tensions between the need for evidence based innovation and the social desire to adhere to stability. It is difficult to talk about Monsanto as agricultural innovative technology provider without touching this topic of emotional loaded controversy.

Brian R. Davis | University of Texas Health Science Center at Houston, USA

Development of stem/progenitor cell-based approaches (editing of human pluripotent stem cells)

Dr. Davis’ laboratory has as its primary objective sequence-specific genetic correction of mutations in stem cells derived from patients with inherited disorders affecting the lung or blood system, with the ultimate goal of developing stem/progenitor cell-based therapeutic approaches. Over the past five years, his laboratory has developed significant expertise in editing the genome of human pluripotent stem cells – either for correction of inherited genetic mutations or for developing lineage- or stage-specific fluorescent reporters to guide the directed in vitro differentiation of hESCs/hiPSCs to specific cell types of interest. In addition, Dr. Davis serves as Director of the Center for Stem Cell and Regenerative Medicine, in which he leads 13 faculty, all of whom have active stem cell-based research programs at various stages of basic or translational development.

Wouter de Laat | Hubrecht Institute, Utrecht, the Netherlands

How genome structure influences genome function (using high throughput 3C and sequencing methods)

The architecture of DNA in the interior of the living cell nucleus is an emerging key contributor to genomic function. Aim of our research is to understand how genome structure influences genome function. We use and develop novel high-throughput sequencing approaches based on chromosome conformation capture and with next and third generation sequencing, which we combine with sophisticated genome-editing strategies to study the interplay between genome folding, epigenetics and gene regulation in mammals and to uncover the proteins that dictate the shape of our genome. In addition, we develop and apply strategies like Targeted Locus Amplification (TLA) technology for targeted analysis of genetic variation and chromosomal alterations, which we apply for example to enable non-invasive prenatal diagnosis (NIPD) of monogenic diseases, such as thalassemia and cystic fibrosis.

Yiliang Ding | John Innes Centre, Norwich, UK

In vivo RNA structure profiling reveals novel mechanisms of post-transcriptional gene regulations

Regulation of RNA levels has garnered much attention in recent years because of its direct and rapid regulation of protein levels. RNA structure plays critical roles in this gene regulation. However, determining RNA structure in vivo has been very challenging. In most cases RNA structures are based on in vitro synthesized RNAs or in silico predictions. Also lack of genome-wide in vivo RNA structural data limits our understanding of how RNAs fold and regulate gene expression globally in vivo. Here, we established several in vivo RNA structure profiling methods at the genome wide scale. The genome wide study reveals native RNA structural features that relate to numerous biological processes in the post-transcriptional gene regulations. These findings will certainly not only open up new avenues for understanding the gene regulations but also provide the new approaches for engineering transcriptome.

Robert Ferl | University of Florida, USA

Plants in the exploration schema – How do we get to the vision?

The study of space biology, along with astrobiology and exobiology, challenges science to actually probe the edges of existence.  Space biology, in particular, invites questions regarding the limits of the adaptive capacity within terrestrial biology as it moves away from Earth. For example, gravity is one of the fundamental tropic forces that impact plant growth and development, and the dissection of gravity-related signaling has been a rich source of insights into the metabolic paths plants take as they respond to changes in their environment.  Changing the gravity vector has long been used in the study of plant tropism (e.g. Darwin and Darwin, 1880, The Power of Movement in Plants), but it was not until the access to space in the mid 1960’s that it was possible to actually take gravity out of the equation. Science can now probe the role of gravity in defining plant biology, and to explore what is truly a novel environment – one that has not been approached in the evolutionary history of plants.  The insights that these experiments have contributed to our understanding of plant processes are varied, complex and extend far beyond gravitropism. In addition, plants have long been considered to be critical components of the long-term exploration life support system in that plants will play a central role in the advanced human life support systems envisioned for long duration spaceflight and extraterrestrial exploration. The challenges of creating suitable plant growth conditions within spaceflight vehicles and extraterrestrial habitats has driven interesting hardware engineering solutions, and those solutions have in turn resulted in tremendous gains in understanding plant biology in the exploration venue.

John Glass | J. Craig Venter Institute, USA

Design, Construction, and Analysis of a Synthetic Minimal Bacterial Cell

The minimal cell is the hydrogen atom of cellular biology. Such a cell, because of its simplicity and absence of redundancy would be a platform for investigating just what biological components are required for life, and how those parts work together to make a living cell.  Since the late 1990s, our team at the Venter Institute has been developing a suite of synthetic biology tools that enabled us to build what previously has only been imagined, a minimal cell. Specifically, a bacterial cell with a genome that expresses only the minimum set of genes needed for the cell to divide every two hours that can be grown in pure culture.  That minimal cell has about half of the genes that are in the bacterium on which it was based, Mycoplasma mycoides JCVI syn1.0, the so-called synthetic bacteria we reported on in 2010. We used transposon bombardment to identify non-essential genes, and genes needed to maintain rapid growth in M. mycoides.  Based on those data, we designed and synthesized a reduced genome in eight overlapping segments. All segments were individually viable when combined with wild type versions of the seven other segments. Combinations of reduced segments that were not viable allowed us to identify synthetic lethal pairs of genes. These occur when two genes each encode an essential function. Those findings required re-design and re-synthesis of some reduced genome segments. Three cycles of design, synthesis, and testing, with retention of quasi?essential genes, produced synthetic bacterium JCVI?Syn3.0 (531 kb, 474 genes), which has a genome smaller than that of any autonomously replicating cell found in nature. Synthetic bacterium JCVI-Syn3.0 retains almost all genes involved in synthesis and processing of macromolecules. Surprisingly, it also contained 149 genes with unknown biological functions, suggesting the presence of undiscovered functions essential for life. This minimal cell is a versatile platform for investigating the core functions of life, and for exploring whole?genome design. Since it was initially reported in 2016, we have identified functions for about 50 of the original 149 genes of unknown function and are in the process of developing a computational model of the cell.

This work was supported by Synthetic Genomics, Inc., DARPA Living Foundries contract HR0011-12-C-0063, and the J. Craig Venter Institute.

Paul Higgs | McMaster University, Canada

Three ways to synthesize an RNA molecule (RNA World): Linking Physics, Chemistry and Biology in the RNA World

According to the RNA World theory for the origin of life, the first replicating molecules were nucleic acids that had the ability to act as both a gene and a catalyst. A self-replicating biological system must have emerged from a non-living chemical system that was able to synthesize a mixture of random sequences. Here, we focus on three different ways that an RNA sequence could be synthesized:

(i) spontaneous polymerization of random RNAs from single nucleotides;

(ii) non-enzymatic replication, where a strand acts as a template for a complementary sequence;

(iii) catalytic replication, where a ribozyme catalyzes the replication of a template strand.

We refer to these as the s, r, and k reactions, respectively. These reactions cross the boundary from non-living to living. The s reaction is non-living chemistry, the k reaction is living biology, and the r reaction falls in the grey area in between. We will discuss both the experimental evidence and the computational models that explain how these mechanisms could have operated, aiming to address the following questions. What physical conditions are needed to enable the formation of long RNA sequences? What physical properties of a biopolymer such as RNA make it a good substrate for replication? How does replication select for ordered properties such as chirality and uniform biopolymer chemistry? How can the first replicating molecules overcome the challenges of deleterious mutations and parasites and evolve towards more complex organisms?

Steve Long | University of Illinois, USA

Bioengineering Photosynthesis.  The Final Frontier in Increasing Sustainable Crop Yield Potential and Ensuring Future Global Food Security.

Demand for our major crops may rise 70-100% by 2050, while we look increasingly to croplands for energy as well as food, feed and urban development.  This is at a time when the increases in yield seen over the past 60 years are stagnating and global change poses a further threat to production.  In reality we have little more than one crop breeding cycle in which to insure against this emerging short-fall.  The approaches of the Green Revolution are now approaching their biological limits.  However, photosynthesis, which is among the best known of plant processes, falls far below its theoretical efficiency, even in our best modern cultivars.  Theoretical analysis and in silico engineering have suggested a number of points at different levels of organization from metabolism to crop canopy structure where efficiency of light, nitrogen and water use could be improved.  It will be shown that this is particularly so in the context of global atmospheric change.  Genetic transformation, both as a means and as a test of concept, have begun to validate some of these suggested improvements with greater production in the field.  Synthetic and systems approaches being used in our BMGF project on Realizing Increased Photosynthetic Efficiency (RIPE) and related projects will be outlined and successes described.

Pier Luigi Luisi | Università degli Studi di Roma Tre, Italy

Minimal cell as models for biological membranes and never born proteins; the origin of functional macromolecules

The necessary qualification is “what is life for science?”.  And, correspondingly, what I will present as an answer is the theory of autopoiesis by Maturana and Varela, the two scientists from Santiago de Chile. They start with the phenomenological observation of the behaviour of a cell, the biological unity of life, emphasizing what is an inherent apparent paradox: that a cell is characterized at each moment by a myriad of internal chemical transformations- but despite this, there is self-maintenance: a liver cell remains a liver cell, an amoeba remains an amoeba, at least for a certain observation time (homeostasis). This apparent paradox- self-maintenance despite the thousands of chemical transformations- is possible because the cell regenerates from within all those compounds which are being consumed away. Of course, autopoiesis is possible thanks to energy and food from the environment: the living cell, as any living system, is an “open system. Thus, life is a factory which re-makes itself (auto-poiesis, namely self-production) from within the boundary (boundary of its own making). A machine, a robot, cannot do this. Autopoiesis is thus the signature of life, whatever is living, must be autopoietic, and vice versa. This simple, basic consideration links to other general features of life, for example that life is a systemic phenomenon, and as such non-localizable into a single reaction or a single chemical (certainly not in the single DNA). The interaction with the environment links to the question of “cognition”.  For the Santiago school, all living organisms are cognitive systems, also bacteria, meaning by that each organism is provided with the “cognitive” physiological tools to recognize and interact with its specific environment-fish with water, earth worm with earth. And this is in turn connected to the important notion of “operational closure”- so that each organism sees the world in its own way. The organism and the environment operate a co-emergence, by which one depends on the other. This brings to the large domain of ecology, and for the individual, to the complex notions of self and consciousness.

Andrei Lupas | MPI for Developmental Biology, Tuebingen, Germany

Evolution of protein folds

For the most part, contemporary proteins can be traced back to a basic set of domain prototypes, many of which were already present in the Last Universal Common Ancestor of life on Earth, around 3.5 billion years ago. The origin of these domain prototypes, however, remains poorly understood. We have proposed that they arose from an ancestral set of peptides, which acted as cofactors of RNA-mediated catalysis and replication1. Initially, these peptides were entirely dependent on the RNA scaffold for their structure, but as their complexity increased, they became able to form structures by excluding water through hydrophobic contacts, making them independent of the RNA scaffold. Their ability to fold was thus an emergent property of peptide-RNA coevolution. 

 The ribosome is the main survivor of this primordial RNA world and offers an excellent model system for retracing the steps that led to the folded proteins of today, due to its very slow rate of change2. Close to the peptidyl transferase center, which is the oldest part of the ribosome, proteins are extended and largely devoid of secondary structure; further from the center, their secondary structure content increases and supersecondary topologies become common, although the proteins still largely lack a hydrophobic core; at the ribosomal periphery, supersecondary structures coalesce around hydrophobic cores, forming folds that resemble those seen in proteins of the cytosol. Collectively, ribosomal proteins chart a path of progressive emancipation from the RNA scaffold, offering a window onto the time when proteins were acquiring the ability to fold.

 We retraced this emancipation from the RNA scaffold for a cytosolic protein fold, the tetratricopeptide repeat (TPR), by amplifying an ??-hairpin from a ribosomal protein, RPS20, which is unstructured in the absence of the cognate ribosomal RNA. We found that this intrinsically disordered peptide could form a folded protein through the increase in complexity afforded by repetition.

William Martin | Heinrich-Heine-Universität Düsseldorf, Germany

Early evolution of microorganisms, geochemical origin of life

Bill Martin works on early evolution. His current work focusses on the reconstruction of important events in early microbial evolution through the investigation of information contained in modern genomes. At the current focus of his work is endosymbiosis in eukaryote evolution, major transitions in microbial evolution, the physiology and habitat of the last universal ancestor (Luca), and the geochemical origin of life. 

Ellen Nisbet | University of Cambridge, UK

Gene expression in a remnant chloroplast: the Plasmodium apicoplast

The Apicomplexa, which include Plasmodium (malaria parasite) and Toxoplasma, contain a single, remnant chloroplast known as an apicoplast. In Plasmodium and other parasitic spieces, the apiocoplast is no longer able to carry out photosynthesis. However, the organelle is essential and is the target of important anti-malarial drugs such as doxycycline, an inhibitor of apicoplast protein synthesis. It retains a small, but functional genome.

We have shown that the primary apicoplast transcripts are polycistronic, followed by extensive RNA processing. Such processing often involves the specific excision of tRNA molecules, allowing the release of mRNA molecules from overlapping genes. We have identified a conserved sequence motif which is associated with RNA cleavage, and show that an apicoplast-targeted protein binds to these sites. We have also found evidence for limited RNA editing. Together, these features allow for the efficient regulation of gene expression in a greatly reduced genome. 

Such RNA processing events are remarkably similar to those that occur in a related group of organisms, the dinoflagellate algae. Dinoflagellate algae are essential symbionts in corals, and their loss (as a result of rising ocean temperatures) causes the death of coral reefs. Thus, discovering the mechanism behing chloroplast transcript processing will not only help us better understand malaria, it will also help us save coral reefs.

Anna-Lisa Paul | University of Florida, USA

The physiological adaptation of plants to spaceflight – navigating in a novel environment

Plants physiologically adapt to spaceflight by changing patterns of gene expression, and the complement of proteins that contribute to the metabolic processes necessary to adjust to this novel environment. Plants grown entirely in a spaceflight habitat develop new strategies, and use new metabolic tools distinct from those grown in terrestrial habitats.  The spaceflight transcriptome does not reflect a response typical of any one terrestrial abiotic stress response of environmental stimulus, nor is it similar to the response to a disruption of gravity by continuous reorientation. Spaceflight appears to initiate cellular remodeling throughout the plant, yet specific strategies of the response are distinct among specific organs of the plant. Although functionally related genes are differentially represented among different organs in the same plant (leaves, hypocotyls, and roots), and even among cultivars, the expression patterns of individual genes representing those functions varies substantially. This observation indicates that there is no single response to spaceflight, rather, each organ, each cultivar, each developmental age, employs its own response tactics within a shared strategy. In addition to examining the global changes in transcriptional patterns, we can also target the behavior of individual genes within individual structures on orbit. Our work with fluorescent reporter gene imaging provides a living window into how plants adapt their physiology to cope with growth in an environment outside of their evolutionary experience.

Mike Snyder | Stanford University, USA

Managing Health and Disease Using Big Data

Understanding health and disease requires a detailed analysis of both our DNA and the molecular events that determine human physiology. We performed an integrated Personal Omics Profiling (iPOP) of 100 healthy and prediabetic participants over four years including periods of viral infection as well as during controlled weight gain and loss. Our iPOP integrates multiomics information from the host (genomics, epigenomics, transcriptomics, proteomics and metabolomics) and from the gut microbiome as well as wearable information. Longitudinal multiomics profiling reveals extensive dynamic biomolecular changes occur during times of perturbation, and the different perturbations have distinct effects on different biological pathways. Wearable data also adds unique early detection information. Overall, our results demonstrate a global and system-wide level of biochemical and cellular changes occur during environment exposures and omics profiling can be used to manage health.

Sarah Teichmann | Sanger Institute, Hinxton, UK

Understanding Cellular Heterogeneity

From techniques such as microscopy and FACS analysis, we know that many cell populations harbour heterogeneity in morphology and protein expression. With the advent of high throughput single cell RNA-sequencing, we can now quantify transcriptomic cell-to-cell variation. I will discuss technical advances and biological insights into understanding cellular heterogeneity in T cells and ES cells using single cell RNA-sequencing.

Olivier Tenaillon | IAME Research Center, Paris, France

Tempo and mode of bacterial adaptation: in vitro, in vivo, in natura

With the rise of antibiotic resistance and the emergence of new forms of virulence, it has become clear that microbial evolution is at the heart of infectious diseases. The aim of our team is to study the microbial adaptation with a quantitative methodology.  For that purpose, we combine four approaches: experimental evolution, comparative genomics, high throughput analysis of mutants and population genetics.