The SkillsCenter: Creating scalable research opportunities for STEM students.

Undergraduate students generally need laboratory skills and experience to be accepted into a position within an academic lab or a company. However, those settings are traditionally where students would develop that necessary expertise. We developed a laboratory course paradigm to equip students with the skills they need to access future opportunities.

How Do Instructors Explain The Mechanism by which ATP Drives Unfavorable Processes?

Concerns regarding students' difficulties with the concept of energy date back to the 1970s. They become particularly apparent for systems involving adenosine triphosphate (ATP), which plays a central role in maintaining the nonequilibrium state of biological systems and in driving energetically unfavorable processes. One of the most well-documented misconceptions related to ATP is the idea that breaking bonds releases energy, when the opposite is true.

Rethinking (again) Hardy-Weinberg and genetic drift in undergraduate biology.

Designing effective curricula is challenging. Content decisions can impact both learning outcomes and student engagement. As an example consider the place of Hardy-Weinberg equilibria (HWE) and genetic drift calculations in introductory biology courses, as discussed by Masel (2012).

Making mechanistic sense: are we teaching students what they need to know?

Evaluating learning outcomes depends upon objective and actionable measures of what students know - that is, what can they do with what they have learned. In the context of a developmental biology course, a capstone of many molecular biology degree programs, I asked students to predict the behaviors of temporal and spatial signaling gradients. Their responses led me to consider an alternative to conventional assessments, namely a process in which students are asked to build and apply plausible explanatory mechanistic models ("PEMMs").

Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins.

Cytoplasmic intermediate filaments (IFs) surround the nucleus and are often anchored at membrane sites to form effectively transcellular networks. Mutations in IF proteins (IFps) have revealed mechanical roles in epidermis, muscle, liver, and neurons. At the same time, there have been phenotypic surprises, illustrated by the ability to generate viable and fertile mice null for a number of IFp-encoding genes, including vimentin.

Whole-Mount Immunocytochemistry in .

To visualize the effects of experimental perturbations on normal cellular behavior, morphology, and intracellular organization, we use a simple whole-mount immunocytochemical method with oocytes, explants, or embryos. This method is applicable to a wide range of systems, including human-induced pluripotent stem cell-derived organoids, and can be used with both chromogenic (horseradish peroxidase/diaminobenzidine) and fluorescent imaging.

TSPAN12 Is a Norrin Co-receptor that Amplifies Frizzled4 Ligand Selectivity and Signaling.

Accessory proteins in Frizzled (FZD) receptor complexes are thought to determine ligand selectivity and signaling amplitude. Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular β-catenin signaling in different CNS structures. In the retina, the tetraspanin TSPAN12 and the ligand norrin (NDP) mediate angiogenesis, and both genes are linked to familial exudative vitreoretinopathy (FEVR), yet the molecular function of TSPAN12 remains poorly understood.

Nuclear roles for cilia-associated proteins.

Cilia appear to be derived, evolutionarily, from structures present in the ancestral (pre-ciliary) eukaryote, such as microtubule-based vesicle trafficking and chromosome segregation systems. Experimental observations suggest that the ciliary gate, the molecular complex that mediates the selective molecular movement between cytoplasmic and ciliary compartments, shares features with nuclear pores. Our hypothesis is that this shared transport machinery is at least partially responsible for the observation that a number of ciliary and ciliogenesis-associated proteins are found within nuclei where they play roles in the regulation of gene expression, DNA repair, and nuclear import and export.

Diagnostic of students' misconceptions using the Biological Concepts Instrument (BCI): A method for conducting an educational needs assessment.

Concept inventories, constructed based on an analysis of students' thinking and their explanations of scientific situations, serve as diagnostics for identifying misconceptions and logical inconsistencies and provide data that can help direct curricular reforms. In the current project, we distributed the Biological Concepts Instrument (BCI) to 17-18-year-old students attending the highest track of the Swiss school system (Gymnasium). Students' performances on many questions related to evolution, genetics, molecular properties and functions were diverse.

The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course.

Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students' ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena.

Identifying domains of EFHC1 involved in ciliary localization, ciliogenesis, and the regulation of Wnt signaling.

EFHC1 encodes a ciliary protein that has been linked to Juvenile Myoclonic Epilepsy. In ectodermal explants, derived from Xenopus laevis embryos, the morpholino-mediated down-regulation of EFHC1b inhibited multiciliated cell formation. In those ciliated cells that did form, axoneme but not basal body formation was inhibited.

Centrin-2 (Cetn2) mediated regulation of FGF/FGFR gene expression in Xenopus.

Centrins (Cetns) are highly conserved, widely expressed, and multifunctional Ca(2+)-binding eukaryotic signature proteins best known for their roles in ciliogenesis and as critical components of the global genome nucleotide excision repair system. Two distinct Cetn subtypes, Cetn2-like and Cetn3-like, have been recognized and implicated in a range of cellular processes. In the course of morpholino-based loss of function studies in Xenopus laevis, we have identified a previously unreported Cetn2-specific function, namely in fibroblast growth factor (FGF) mediated signaling, specifically through the regulation of FGF and FGF receptor RNA levels.

Chibby functions in Xenopus ciliary assembly, embryonic development, and the regulation of gene expression.

Wnt signaling and ciliogenesis are core features of embryonic development in a range of metazoans. Chibby (Cby), a basal-body associated protein, regulates β-catenin-mediated Wnt signaling in the mouse but not Drosophila. Here we present an analysis of Cby's embryonic expression and morphant phenotypes in Xenopus laevis.

The trouble with chemical energy: why understanding bond energies requires an interdisciplinary systems approach.

Helping students understand "chemical energy" is notoriously difficult. Many hold inconsistent ideas about what energy is, how and why it changes during the course of a chemical reaction, and how these changes are related to bond energies and reaction dynamics. There are (at least) three major sources for this problem: 1) the way biologists talk about chemical energy (which is also the way we talk about energy in everyday life); 2) the macroscopic approach to energy concepts that is common in physics and physical sciences; and 3) the failure of chemistry courses to explicitly link molecular with macroscopic energy ideas.

Turning randomness into meaning at the molecular level using Muller's morphs.

While evolutionary theory follows from observable facts and logical inferences (Mayr, 1985), historically, the origin of novel inheritable variations was a major obstacle to acceptance of natural selection (Bowler, 1992; Bowler, 2005). While molecular mechanisms address this issue (Jablonka and Lamb, 2005), analysis of responses to the Biological Concept Inventory (BCI) (Klymkowsky et al., 2010), revealed that molecular biology majors rarely use molecular level ideas in their discourse, implying that they do not have an accessible framework within which to place evolutionary variation.

sizzled function and secreted factor network dynamics.

Studies on the role of the E-box binding transcription factor Snail2 (Slug) in the induction of neural crest by mesoderm (Shi et al., 2011) revealed an unexpected increase in the level of sizzled RNA in the dorsolateral mesodermal zone (DMLZ) of morphant Xenopus embryos. sizzled encodes a secreted protein with both Wnt and BMP inhibitor activities.

A maternally established SoxB1/SoxF axis is a conserved feature of chordate germ layer patterning.

Despite deep evolutionary roots in the metazoa, the gene regulatory network driving germ layer specification is surprisingly labile both between and within phyla. In Xenopus laevis, SoxB1- and SoxF-type transcription factors are intimately involved in germ-layer specification, in part through their regulation of Nodal signaling. However, it is unclear if X.

Using graph-based assessments within socratic tutorials to reveal and refine students' analytical thinking about molecular networks.

Biological systems, from the molecular to the ecological, involve dynamic interaction networks. To examine student thinking about networks we used graphical responses, since they are easier to evaluate for implied, but unarticulated assumptions. Senior college level molecular biology students were presented with simple molecular level scenarios; surprisingly, most students failed to articulate the basic assumptions needed to generate reasonable graphical representations; their graphs often contradicted their explicit assumptions.

Snail2 controls mesodermal BMP/Wnt induction of neural crest.

The neural crest is an induced tissue that is unique to vertebrates. In the clawed frog Xenopus laevis, neural crest induction depends on signals secreted from the prospective dorsolateral mesodermal zone during gastrulation. The transcription factors Snail2 (Slug), Snail1 and Twist1 are expressed in this region.

Mechanisms driving neural crest induction and migration in the zebrafish and Xenopus laevis.

The neural crest is an evolutionary adaptation, with roots in the formation of mesoderm. Modification of neural crest behavior has been is critical for the evolutionary diversification of the vertebrates and defects in neural crest underlie a range of human birth defects. There has been a tremendous increase in our knowledge of the molecular, cellular, and inductive interactions that converge on defining the neural crest and determining its behavior.

Regulation of TCF3 by Wnt-dependent phosphorylation during vertebrate axis specification.

A commonly accepted model of Wnt/β-catenin signaling involves target gene activation by a complex of β-catenin with a T-cell factor (TCF) family member. TCF3 is a transcriptional repressor that has been implicated in Wnt signaling and plays key roles in embryonic axis specification and stem cell differentiation. Here we demonstrate that Wnt proteins stimulate TCF3 phosphorylation in gastrulating Xenopus embryos and mammalian cells.

Unexpected functional redundancy between Twist and Slug (Snail2) and their feedback regulation of NF-kappaB via Nodal and Cerberus.

A NF-kappaB-Twist-Snail network controls axis and mesoderm formation in Drosophila. Using translation-blocking morpholinos and hormone-regulated proteins, we demonstrate the presence of an analogous network in the early Xenopus embryo. Loss of twist (twist1) function leads to a reduction of mesoderm and neural crest markers, an increase in apoptosis, and a decrease in snail1 (snail) and snail2 (slug) mRNA levels.

Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe.

Epithelial-mesenchymal transition (EMT) describes a series of rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell-cell adhesion structures, alter their polarity, reorganize their cytoskeleton, and become isolated, motile, and resistant to anoikis. The term EMT is often applied to distinct biological events as if it were a single conserved process, but in fact EMT-related processes can vary in intensity from a transient loss of cell polarity to the total cellular reprogramming, as found by transcriptional analysis.