iBiology Podcast

What is the consequence of obesity in human health? Physically, obesity can result in lower mobility and sleeping disorders. But, in humans, the link between obesity and metabolic diseases isn’t straightforward. For example, not everyone that’s obese becomes insulin resistant. As O’Rahilly explains, the probability of an obese individual to have a metabolic disease is linked to the capacity of adipose tissue to store the extra fat. Mutations that decrease fat storage in adipose tissue increase the chance of metabolic diseases, like insulin resistance, even when the person is not obese.

Easy access to nutrients has contributed to the increase in obesity in the human population. But, what is obesity and why isn’t everybody fat? Dr. Stephen O’Rahilly provides a biomedical perspective of obesity, and evaluates which genes could potentially shift the balance towards obesity. As he explains, one becomes obese when the balance between energy intake and energy spent is shifted. Surprisingly, mutations that lead to obesity in humans aren’t in genes involved in metabolism and energy storage, but failure in satiety signals in the brain that result in people eating too much. The excess of energy intake over energy expenditure leads to obesity.

The severity of malarial disease is influenced by interactions between the parasite, the host and environmental factors. In her third talk, Mota explains how her lab used a mouse model to study the impact of host nutritional status on disease severity. When they compared infections in calorically restricted (CR) mice and freely fed mice, they found less reproduction of the malaria parasite and a lower parasite load in CR mice.  This suggested that Plasmodium are able to sense and respond to host nutritional status.  Mota describes how her lab identified a key Plasmodium kinase, KIN, that seems to regulate parasite response to nutrient availability and may provide a target for antimalarial drugs.

In Part 2, Mota goes into more depth about the liver stage of malaria infection.  She reminds us that when Plasmodium parasites are transferred by a mosquito bite, they first travel to the liver. Once inside of a hepatocyte, a single malaria parasite will replicate and give rise to over 10,000 new parasites that go on to infect red blood cells and cause disease.  For many years, this stage was called the silent stage as it was thought that malaria parasites were not detected by the host while in the liver. Mota tells us about data from her lab, and others, showing that the host innate immune response is, indeed, activated during hepatocyte infection. This immune response may play a role in modulating the host’s response to the blood-stage infection or future re-infection.

Malaria is currently responsible for about 500,000 deaths per year and is especially fatal to children under the age of 5 years.  Two global eradication programs since 1950 have reduced the malaria burden significantly, however, progress has stalled in recent years.  In her first talk, Dr. Maria Mota details the lifecycle of two malaria parasites, Plasmodium falciparum and P. vivax. The complex, multistage lifecycle makes it hard to diagnose and treat malaria. Mota explains that many attempts have been made to treat the disease with drugs but the malaria parasite very rapidly develops resistance.  She describes how the recent development of drug combinations and a new vaccine, together with insecticide treated bed nets and improved early diagnosis, provide hope for better prevention and treatment of malaria in the future.

Almost every person in the world has been bitten by a blood feeding insect or arthropod, such as a mosquito or tick. Yet, most of us haven’t thought much about arthropod saliva. The molecules found in the saliva of blood feeders play a role in disease transmission and immune recognition. Therefore, it is important to better understand what makes up arthropod saliva. Dr. Mondragon-Shem begins her seminar by describing the phenomenon of red meat allergy, and how it was historically linked to tick bites. She then shares her research findings that confirm the presence of alpha-Gal sugar, the immunogenic molecule that leads to red meat allergy, in tick saliva. Her studies also identified protein candidates that are likely linked to alpha-Gal in tick saliva. Dr. Mondragon-Shem finishes her talk by describing how she has characterized the sugar molecules in the saliva of six species of blood feeding arthropods. This work has implications for better understanding disease transmission and immune recognition.

In 1953, Watson and Crick proposed a double-helical structure for DNA and suggested that it replicated in a semi-conservative manner. This method of replication was not universally accepted as correct, however. In this talk, Meselson recalls the events that led him to meet Frank Stahl and to plan and execute the now famous experiment proving that DNA does indeed undergo semi-conservative replication.

In her second talk, Lehmann focuses on the establishment of the dichotomy between somatic and germ line fate. She explains how Drosophila germ cells develop to become so different from the somatic cells that make up the rest of the embryo. Germ cell development depends solely on maternal transcripts from the egg, while development of the soma depends on new zygotic transcription.  Lehmann describes how two different molecular strategies, precise spatially controlled protein degradation and complete interference with the mRNA transcriptional elongation process, are employed to prevent somatic differentiation, thus allowing germ cell specific gene expression to occur.

Very early in embryogenesis, germ cells, the cells that give rise to egg and sperm, are set aside from the somatic cells which give rise to the rest of the cells in our bodies. While germ cells are not necessary for survival of the individual, they are crucial for survival of the species. In her first talk, Dr. Ruth Lehmann explains that there are two mechanisms by which germ cells are specified in the early embryo; via germ plasm or via induction.  Germ cells specified via either mechanism have in common the presence of germ granules; large, membraneless, ribo-nuclear particles. Interestingly, certain families of RNA regulatory proteins are conserved in germ granules across species. Lehmann describes work from her lab and others on the life cycle of germ granules in Drosophila, including how they are assembled, their interesting biophysical properties and how proteins and RNAs are organized within the granules.

To better understand how an entire embryo develops from a single cell, Dr. Philipp Keller and colleagues developed a technique to image and quantitatively reconstruct mouse embryogenesis from gastrulation through early organogenesis at the single-cell level. Keller’s lab developed an adaptive light-sheet microscope to follow the mouse embryo for 48 hours while it’s developing its germ layers (mesoderm, endoderm, and ectoderm), early tissues, and organs. By combining long-term high-resolution imaging, computational, and statistical analyses, they generated a dynamic fate map of the embryo. These open-access resources aid in the understanding of the dynamic cell behaviors that allow for proper growth and development of the embryo.