iBiology Podcast

Have you ever tried to catch a flying fly only to be frustrated by their ability to evade your efforts? Then you know that many insects are extremely agile fliers. In his three talks, Dr. Michael Dickinson uses aerodynamics, muscle physiology, and neuroscience to explain how flies fly.

In Part 1, Dickinson focuses on lift. How do insects generate the aerodynamic forces necessary to stay in the air? Dickinson explains that by studying high speed videos of flies in flight, it is possible to determine the motion of the wing at each moment in time and, from that information, determine the forces that the insect is generating during an entire wing stroke. Early studies of this type calculated that insects did not generate enough force to keep them in the air! So how do flies fly? To answer this question, Dickinson and colleagues built a large scale robotic model of an insect wing moving through a viscous solution. Video tape of these models showed that the wing can form a large vortex at its leading edge. This vortex augments the forces generated by the insect and provides enough lift to keep the insect in flight. By changing the angle of attack of the wing, the fly can change the size of the leading edge vortex and how much lift is produced.

In Part 3, Dickinson discusses how insects control flight. Insects have many sensors on their bodies and wings that detect odors, the polarization of light, body rotation, air movement, and more. All of this sensory information is taken in and integrated by the insect’s brain. The brain then regulates muscle function to perform the behaviors needed for the fly to survive in its natural environment. Dickinson and his colleagues have built “arenas” in which a fly can be tethered and visual cues can be used to make the fly think it is flying in a specific direction with a certain speed, or being attacked by a predator. Using high speed video, it is possible to measure the flies response to these visual cues. Amazingly, within 20 milliseconds of detecting a predator, a fly can integrate its response so that it completely changes flight direction and flies away from the perceived predator.

Dickinson’s second talk focuses on power.  Small insect wings must beat very rapidly – much more quickly than can be controlled by the release and uptake of Ca2+ that typically regulates muscle contraction.  Instead flies use two sets of stretch activated power muscles. The contraction of downstroke muscles stretches and stimulates upstroke muscles, and vice versa, allowing the insect to beat its wings very quickly. In addition to power muscles, insects have tiny steering muscles that connect directly to the wing and regulate wing deviation during the wing stroke. With a combination of high speed video and electrical recording, Dickinson demonstrates how these tiny muscles can change wing position and allow a fly to undergo its amazing aerial acrobatics.

In her second talk, Churchland outlines her group’s studies of the relationship between decision-making and action. She notes that in addition to methods to track neural activity, high-resolution videos of the decision-making process in mice provide valuable movement data. Using labeled calcium to visualize neural activity across the dorsal cortex, Churchland’s group finds that maps of the visual world are represented up to six times in each mouse brain! The Churchland group also found that neural activity appeared to be the same across novice and expert decision-makers. They developed a mathematical model to predict the influence of numerous variables on neural activity and found that movement-related variables accounted for a greater proportion of the variance in neural activity than decision-related variables. Specifically, spontaneous (non-instructed) movements had the greatest predicted influence on neural activity. They then validated their results at the single-neuron level using two-photon microscopy. Dr. Churchland ends her talk by highlighting a significant remaining question: what are the neural differences between novice and expert decision-makers?

How do brains make decisions? In this seminar, Dr. Anne Churchland tells us why understanding decision-making is important, and outlines common approaches to study decision-making in the lab using a variety of mammals. She describes findings that suggest accurate decision-making results from a combination of visual and auditory stimuli in both humans and rats, and tells of the discovery of an explore-exploit tradeoff that allows rats to respond optimally to changing environments. Dr. Churchland then outlines the major methods for tracking neural activity in the brain and shows how they have been used to determine that many brain areas are active during decision-making. She ends her talk with an overview of new directions in the field.

Christofferson also works on characterizing understudied arboviruses like Bunyamwera, Batai, and Ngari, all of which are orthobunyaviruses. First, in the laboratory, her lab studied the growth of these Orthobunyaviruses in-vitro and investigated a mouse model to determine the cross-reactivity of these viruses. In addition, in collaboration with scientists in Rwanda, Christofferson investigated whether Bunyamwera, Batai and Ngari circulated in the country, and caused disease in cattle. As Christofferson explains, a better understanding of the prevalence of viruses that affects the cattle may alleviate misdiagnosis and allows us to follow the possible emergence of newly detected viruses.

In her second talk, Christofferson uses the Aedes aegypti-Zika system to explain how mosquito-life traits can be used to understand the process of vector competence. Zika is an arbovirus that is transmitted to humans via the Aedes aegypti mosquito. Christofferson measures how much time it takes for a mosquito to become infectious after its initial exposure (extrinsic incubation period) in order to understand how mosquito age interacts with the viral fitness measure of vector competence. This is done in the context of a commonly used mathematical framework, vectorial capacity.

In this talk, Dr. Rebecca Christofferson provides an overview of arboviruses, arthropod-borne viruses, like dengue. Arthropods, such as mosquitoes, act as vectors to transmit diseases to vertebrates, including humans. Christofferson studies arthropod-virus-vertebrate interactions and how environmental factors affect disease transmission. For example, she explains how environmental factors, like changes in temperature and drought, affect the intrinsic ability of a vector to transmit a pathogen (vector competence).

In his Part 3, Chang reminds us that every lncRNA gene has its own set of DNA regulatory elements, such as enhancers and promoters. These regulatory elements can confer functionality to lncRNA genes. Chang shares the research story of a mysterious lncRNA known as PVT1, which is frequently co-amplified with the proto-oncogene MYC in human cancers. His group found that PVT1 promoter activity is inversely correlated with MYC expression – when one is up, the other is down. Finally, Chang shows that the PVT1 and MYC promoters compete for four enhancers located within the PVT1 gene locus.

In his Part 2, Chang introduces long noncoding RNAs, or lncRNAs. As their name suggests, lncRNAs are not translated into proteins, and initially their functions were poorly understood. Chang’s group has developed technologies to better understand the function of lncRNAs. For example, his lab characterized the protein partners that interact with Xist, a canonical lncRNA that mediates X chromosome inactivation. They found that the protein Spen is necessary for X chromosome silencing. Interestingly, Spen has likely been co-opted by mammalian cells to inactivate the X chromosome via viral mimicry.