iBiology Videos

Modern microscopy produces large multi-dimensional datasets, which creates new challenges for data storage, processing and visualization. In this talk, Dr. Loic Royer uses a developing drosophila melanogaster embryo to explain how to solve some of the challenges produced by multi-dimensional microscopy datasets.

In order to understand an image of a biological sample and what it represents, one needs to understand its metadata. Metadata is the information behind the image that shows the experimental procedure, image acquisition settings, and the analysis performed on the data in order to obtain the represented image. Dr. Jason Swedlow explains what constitutes image metadata, and provides examples on how to catalog, organize, analyze, and share the metadata of biological images.

Microscopy is a key technology driving biological discovery. Nowadays, microscopy based scientific findings must be substantiated by quantitative image analysis. The discipline concerned with such quantification of biological microscopy images is called bioimage analysis. Dr. Christian Tischer walks us through the main concepts of a typical bioimage analysis workflow. He explains how to quantitatively interpret the content of microscopy images and how to automatically detect objects in images and derive object based measurements. He also emphasizes the importance of visual inspection and quality control of automated image analysis. Finally, he presents an overview of current bioimage analysis tools and communities.

How do we visualize biological samples? In this talk, Dr. Nico Stuurman provides an overview of the different tools, equipment, and software available to acquire an image of a biological sample using a light microscope, and the considerations one needs to take when using these tools. This lecture will allow scientists to understand the principles behind image acquisition in order to improve and optimize the analysis of their sample.

Just a few months after Tysabri was approved for MS treatment, two patients developed progressive multifocal leukoencephalopathy (PML), a fatal or seriously debilitating disease.  In his second talk, Yednock describes the response of medical and regulatory groups and researchers to this discovery and its impact on the treatment of MS patients with Natalizumab/Tysabri.

Yednock relates the discovery and development, over 15 years, of the drug Tysabri, an alpha4 integrin antibody, as a treatment for multiple sclerosis.

In the first of his two talks, Ted Yednock begins with an overview of multiple sclerosis.  He describes how, in MS, immune cells are able to transverse the wall of blood vessels and infiltrate the brain and central nervous system resulting in damage to the myelin surrounding neurons.  Yednock and his colleagues hypothesized that by blocking the infiltration of immune cells into the brain, the progression of the disease might be slowed.  They went on to identify alpha4 integrin as the molecule that mediates adhesion of immune cells to the blood vessel wall, and they found that an alpha4 integrin antibody (Natalizumab or Tysabri) could block infiltration of the blood cells into the brain in a animal model of MS.  Yednock then details the clinical development of Tysabri through to its approval by the FDA in 2004.

Robert Bhisitkul and Tejal Desai describe how treatment for retinal diseases leading to vision loss, such as age related macular degeneration, may be much improved by efforts to develop implantable devices for drug delivery.

Age related macular degeneration (AMD) is one of several retinal diseases that can lead to vision loss and, ultimately, blindness. Dr. Bhisitkul explains that the class of anti-VEGF biologic drugs (Lucentis, Avastin, Eylea) can treat AMD, however, ongoing, monthly injections into the eye are required for the drugs to be fully effective. There are a number of drawbacks to this treatment regime, many of which could be mitigated by the development of a drug delivery device for implantation in the eye. Dr. Desai describes the work done in her lab to develop an injectable, biocompatible and biodegradable device that has the right release kinetics to successfully deliver needed drugs to the retina of patients with AMD.

Drug discovery for diseases of the nervous system is difficult. Although mouse models are helpful to study many human diseases, they have serious limitations for understanding neurological and psychiatric disease. Dolmetsch describes a method developed by his group to produce induced pluripotent stem cell-derived neurons from patients. Using these iPSC neurons, they can identify molecular defects associated with a neurodevelopmental disease and then identify medicines to treat those diseases.

MS begins as a disease of intermittent episodes with recovery in between. With time, however, MS changes to a progressive disease with increasing disability.  In her talk, Dr. Stadelmann explains that studies of MS brain lesions have identified specific changes that occur with disease progression. For example, chronic MS lesions contain many fewer oligodendrocytes than do early lesions.  Since oligodendrocytes produce the myelin sheath that surrounds axons, drugs that stimulate the migration and establishment of oligodendrocytes in lesions may increase axonal remyelination and improve the prognosis of MS patients. Stadelmann also explains that brain lesions can be caused by conditions other than MS, such as neuromyelitis optica.  Improved studies will help to correctly diagnose and treat these distinct diseases.

Multiple sclerosis (MS) is a debilitating autoimmune disease in which immune cells infiltrate the central nervous system and attack the myelin sheath surrounding axons.  Dr. Simons explains that myelin is necessary for signal conduction by nerve cells and for the metabolic support of axons. Demyelination results in axonal loss and formation of lesions in the brain. A small percentage of MS lesions are capable of remyelination following steps similar to axonal myelination during normal development.  Since lesion remyelination correlates with reduced neurodegeneration, Simons and his colleagues strive to understand why remyelination occurs in only a small number of MS patients and to identify drugs that may promote it.