Part 1: Rooney-Varga explains that a holistic, systems thinking approach is necessary to understand human-caused climate change.  Systems thinking concepts that are critical to climate change science include the accumulation of atmospheric stocks of greenhouse gases, feedback processes that amplify or dampen the impacts of climate change, abrupt nonlinear change, and the delayed impacts of today’s actions, such as emissions today that will influence the climate for millennia.

This is the story behind the discovery of polynucleotide hybridization. In the early 1950s, the double helix structure of DNA had just been published, however, the structure of RNA was still unknown. Alexander Rich and his colleagues were investigating this question without much success until Rich combined polyadenylic acid and polyuridylic acid and, to his amazement, saw the diffraction pattern of a double helix. He realized that the base pairs had undergone hybridization to form a double stranded RNA structure. In the intervening 60 years, hybridization has become the foundation of much of modern biotechnology.

Many animals are able to regenerate following injury, some better than others. Dr. Reddien uses Planaria as a model system to investigate the cellular and molecular mechanisms that drive regeneration. RNAi makes it possible to inhibit specific genes in Planaria and follow the effects on protein expression and regeneration. Using this methodology, Reddien’s lab identified the notum gene as a regulator of the wnt signaling pathway for determining appropriate head or tail regeneration.

In his second talk, Peters presents evidence that cohesin is indeed necessary for genomic DNA to fold into loops. Long range DNA interactions such as loops can be detected using a technique called Hi-C. Using Hi-C, Peters shows that depleting cohesin removes DNA loops, while depleting the proteins that remove cohesin from DNA, results in bigger DNA loops. In addition, CTCF appears to recognize specific sequences that define the base of the loops.  Incorporating all of this data, Peters describes a model in which DNA is extruded by cohesin to form a loop and the boundaries of the loop are determined by CTCF. Peters explains that many questions about the mechanism of DNA loop extrusion and its importance in cells remain to be answered.

It has been known for many years that the protein cohesin is necessary to join sister chromatids together before they are segregated during mitosis.  Electron micrographs have shown that cohesin subunits form a ring complex which is thought to encircle the DNA keeping the chromatids together. When they need to separate during anaphase, the cohesin complex is removed by another set of proteins.  In his first talk, Dr. Peters explains how observations that he and others made suggested that cohesin may have additional roles in the cell. For instance, cohesin is initially loaded onto chromosome arms at discrete sites and in much larger amounts than is needed for chromatid cohesion. Cohesin also was shown to co-localize on chromosomes with a DNA binding protein called CTCF. CTCF is known to regulate transcription by forming DNA loops.  Peters explains that, taken together, these observations hinted at a role for cohesin and CTCF in folding DNA into loops to allow efficient packing of very large eukaryotic genomes into small cell nuclei, and regulating functions such as gene expression.

In his third talk, Patel explores the function of additional Hox genes in the development of crustacean body plans. Using CRISPR-Cas9 genome editing, his laboratory has characterized the expression and function of six of the nine Hox genes in Parhyale, and describes the combinatorial role of Ubx, abdA, and AbdB in the development of specialized appendages in this species, and how changes in the regulation of abdA is responsible for several morphological transitions during crustacean evolution.

In the second lecture, Patel describes the work of his lab to expand the studies of Hox gene function to other arthropods.  Patel describes the development of specialized body parts in crustaceans, and describes the transition between feeding to locomotor appendages. Using the beach hopper, Parhyale, his laboratory, in collaboration with the laboratory of Michalis Averof, showed that Ubx controls the boundary and transition between feeding and locomotor appendages during development.

Homeotic (Hox) genes are transcription factors that dictate the development and compartmentalization (regionalization) of body parts in animals along the anterior-posterior (head to tail) axis. Using various insects and crustaceans, Dr. Nipam Patel studies how alterations in the expression of Hox genes could explain the evolution of specialized body parts in arthropods. Patel describes the spatially restricted patterns of Hox gene expression, explains the effects of Hox gene deletions, and how these phenotypes help us understand the manner in which Hox genes act to control the insect body plan. Taking a closer look at the pattern of the Hox gene Ultrabithorax (Ubx) in different insects, Patel summarizes the discovery that what drives changes in the number of wings during insect evolution is the not changes in the expression pattern of Ubx, but the regulation of its downstream gene targets.

Dr. Vivek Mutalik highlights current challenges in synthetic biology and explains some of the solutions being implemented to address them. Mutalik discusses some of the elements that make current approaches to synthetic biology unpredictable and expensive, and reviews possible ways to move the field forward, including the development of standardized parts with predictable behaviors, robust methods of biocontainment and software that allows data sharing and visualization.

In her second seminar, Parast explains the different models to study human placental development in-vitro. Scientists can derive induced pluripotent stem cells (iPSCs) from umbilical cord cells. Parast’s laboratory first differentiates the iPSCs into trophoblasts cells which can then generate the different cells found in the placenta. Her laboratory uses these placental cells to study developmental complications by comparing cells derived from normal pregnancies to cells derived from non-normal pregnancies (e.g. patients born from mothers with pre-eclampsia).