Knoblich describes experiments in his lab to develop 3 dimensional brain organoids from human pluripotent stem cells. While studying the development of rodent brains has proved extremely useful, there are some important developmental differences that require human tissue for investigation. In addition, some diseases such as microcephaly cannot be modeled in mice. Knoblich and his colleagues have developed cerebral organoids that mimic early human brain development and can be used to model neurodevelopmental disorders. They have also been able to generate separate organoids from various regions of the human brain and then fuse them and follow the migration of live neurons between these parts, opening the path to many more studies of neuronal development.

Dr. Knoblich begins his talk by explaining the key role that asymmetric cell division plays in development of the human brain. During mammalian brain development, neuronal progenitor cells initially divide symmetrically to increase their numbers. Later they divide asymmetrically to produce one progenitor cell and one (or two) cells which will terminally differentiate to become neurons. What determines which daughter cell will become which? Working in Drosophila, Knoblich and others elucidated a signaling pathway in which Par proteins are asymmetrically localized before cell division. This recruits a complex of proteins which defines the orientation of the mitotic spindle and causes the localization of Numb protein at one pole of the cell. Upon cell division, only one daughter cell will inherit Numb protein and this ultimately will determine the fate of the daughter cells. Interestingly, this signaling pathway is conserved from insects to mammals, however, Knoblich found an important difference that may explain why humans have many more cortical neurons than mice.

Since little is known about the Toxoplasma gondii genome, in his second iBiology seminar, Lourido explains how his lab developed CRISPR tools to study apicomplexan biology. His lab designed a strain of T. gondii constitutively expressing Cas9 that can be used in conjunction with guide libraries to identify biologically significant genes. Lourido explains how his lab used this system to identify genes encoding proteins necessary for apicomplexan invasion. These include a claudin-like protein, that they are calling CLAMP, that is conserved across apicomplexa and is necessary for invasion by both toxoplasma and the parasites that cause malaria.  

In a peer-discussion, do well-prepared students simply tell other students the answer?

Bill Wood (University of Colorado Boulder) describes the Smith et al. study, which examines whether students who change their mind as a result of peer-discussion have actually learned the concepts being tested.

Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.

Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.

Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.

Proteins such as signaling molecules, catalytic enzymes, and membrane transporters are not static but are in a state of constant motion for function. In her first talk, Dorothee Kern explains how she uses techniques such as nuclear magnetic resonance (NMR), X ray crystallography, single molecule FRET and computational simulations to visualize rapid protein dynamics. Kern walks us through the basics of these techniques and explains how they can provide structural and energetic information about a protein and how it functions in the cell.

Gleevec (Imatinib) is a very effective drug for treating chronic myelogenous leukemia. It acts by binding to and inhibiting the signaling molecule Abl kinase with extreme specificity. Abl kinase is very closely related to Src kinase, and, in fact, the drug binding pocket for Gleevec is almost identical between the two proteins. Interestingly, however, Gleevec binds to Abl 3000 fold more tightly than it does to Src. Why? In her second talk, Kern answers this question. Her lab used NMR, and the techniques she described in Part 1, to show that the protein dynamics of Abl and Src are dramatically different when Gleevec is bound. In a clever experiment in which they synthesized proteins that were likely evolutionary ancestors of Src and Abl, Kern’s lab was able to show how changes in amino acids throughout the kinases determined the differential binding affinity of Gleevec for Abl kinase over Src kinase. Experiments such as these demonstrate the importance of understanding protein dynamics at the atomic level of the whole protein, not just the drug binding site, when designing new drugs.

Ion channels are crucial for proper neuronal communication and cellular homeostasis. But, how do ion channels perform their work? In this seminar, Dr. Lily Jan defines the physiological role of potassium channels in the generation of an action potential and regulation of excitability in neurons. She outlines the role of voltage-gated and inward-rectifier potassium channels and provides evidence of the evolutionary importance of these proteins.