Dr. Randy Schekman overviews the secretory pathway and reviews historical experiments that shaped our molecular understanding of this pathway. The journey begins at the endoplasmic reticulum (ER), where proteins that engage the secretory pathway get translated. The mRNA of these proteins codes for a signal sequence that serves as a “tag” to bring the mRNA-ribosome-newly-synthesized protein to the ER for continued translation and movement of the new secretory protein across the ER membrane into the interior or lumen of the organelle. Vesicles transport the recently translated proteins to the Golgi Apparatus, where they get “packaged” and sent to their final destination.

Schekman explains how his laboratory used baker’s yeast to uncover major proteins involved in the secretory pathway, and describes proteins involved in budding, vesicle trafficking, and vesicle fusion.  Schekman also presents data from his laboratory that helped to identify the ER channel through which proteins enter the secretory pathway. These series of experiments show how, step by step, scientific knowledge evolves, uncovering the fundamental mechanisms to better understand human disease.

Ramakrishnan’s laboratory has studied the molecular pathogenesis of TB using the power of forward genetics in the zebrafish. They discovered that mutations in LTA4H, a key enzyme in the eicosanoid pathway that alters the levels of the cytokine tumor necrosis factor (TNF), affect tuberculosis pathogenesis by regulating the inflammatory response. This work showed that a balance of TNF is required for good TB prognosis, and neither high nor low inflammation was favorable. Correspondingly, they showed that genetic variation in LTA4H in humans helps explain patterns of TB meningitis survival when patients were exposed to a treatment that suppresses the inflammatory response.

In this seminar, Dr. Lalita Ramakrishnan gives an introduction to tuberculosis (TB) pathogenesis, and gives an overview of Mycobacterium tuberculosis’ life cycle. She explains how the TB bacteria gain entry into the host by using specific lipids to avoid microbicidal macrophages and recruit growth-permissive ones. Once inside the macrophage, the bacteria use multiple virulence genes to survive intracellularly. In particular, Ramakrishnan discusses bacterial efflux pumps that, in addition to promoting intracellular survival, also induce tolerance to multiple antibiotics. Most individuals have effective counterstrategies so that they are able to clear TB infection by a combination of innate and adaptive immunity. Yet scientists have not been able to understand these defense strategies enough to harness them and create an effective vaccine against TB.

After the TB bacteria infect macrophages, a complex structure called a granuloma develops. Different immune cells arrive at the granuloma to surround the bacterial infection and fight the disease. In her second lecture, Ramakrishnan explains how her laboratory used a zebrafish model of TB to study the involvement of granulomas in TB progression. Although granulomas were thought to constrain infection, her laboratory showed that the bacteria hijack the granulomas to spread the disease. For example, Ramakrishnan showed that TB bacteria promote the recruitment of new macrophages to the granuloma that engulf dying infected macrophages to expand infection.

Pringle explains how one can use a “reverse ecology” approach to describe and characterize different organisms and their habitats, by studying their genes. Her laboratory used this approach to study the origins of the Bay Area Amanita phalloides. Although Amanita phalloides was thought to be an invasive species, historical records were mostly descriptive and hard to use as concrete evidence of the species’ biogeography. Using genetic information, the Pringle laboratory was able to definitively prove that early samples identified as Amanita phalloides in the US are distinct from the European species. They also used molecular data to document the symbiotic associations between Amanitaphalloides and plants, proving the efficacy of these approaches to study species that are hard to grow in the lab.

Pringle provides an overview of convergent interactions, defined as the independent emergence of multi-species interactions with similar physiological or ecological functions. For example, multiple plant lineages have independently evolved interactions with fungi in order to exchange resources and form what are known as mycorrhizal symbioses. To further understand how convergent interactions are formed, the Pringle laboratory studied the evolution of plants that have “pitcher”-like structures as well as the mycorrhizal symbiosis in the Amanita genus.

Although people usually relate fungi with diseases, Dr. Anne Pringle provides an overview of the vastly diverse and complex world of fungi, and provides examples of the beneficial roles that fungi have on Earth. For example, although some fungi have been associated with devastating infections that threaten harvests every year, other fungi are mutualists needed for the healthy development of plants and animals.

How is butterfly color created? In this lecture, Aaron Pomerantz takes us on a journey through the Amazon rainforest, where interesting observations about butterfly color and patterns lead him to use imaging and genetics to decode butterfly color.

This talk is part of the Young Scientist Seminars, a video series produced that features young scientists giving talks about their research and discoveries.

Ploegh describes how his lab takes advantage of the unique properties of antibodies from the Camelidae family (alpacas, llamas, camels, etc). In addition to traditional antibodies, these animals naturally make small, heavy-chain only antibodies (nanobodies). These molecules can be isolated, amplified in bacteria, and engineered for new applications. As well as using nanobodies to target viruses and inflammasomes, Ploegh explains how his lab uses labelled nanobodies for non-invasive, live imaging of cancer tumors in mice. These technologies have exciting implications in basic and biomedical studies.