Simons Foundation

Depression is a common, chronic, and debilitating disease. Although many patients benefit from antidepressant medications or other therapies, only about half show complete remission. Factors that precipitate depression, such as stress, are incompletely understood. We have used chronic social defeat stress as an animal model of depression. Prolonged exposure to an aggressor induces lasting changes in behavior such as social avoidance and anhedonia-like symptoms, which are reversed by chronic (but not acute) treatment with available antidepressants.

Dr. Schadt provides an overview of how his team organizes very large scale data across many different types, and then integrates these data using sophisticated mathematical algorithms to construct predictive network models of disease, and discusses the application of this type of modeling in the cancer arena.

In the disease retinitis pigmentosa (RP), disease genes directly cause the dysfunction and death of rod photoreceptors, the photoreceptor type that mediates vision in dim light, causing night blindness. Subsequently, the cone photoreceptors, which mediate color and daylight vision, also lose function and die. Dr. Cepko et al have suggested a model wherein cones are affected due to the dysregulated metabolism that follows rod death. They have begun to develop gene therapy to combat this, using adenovirus-associated vectors (AAV) to deliver genes that help cones fight oxidation and other forms of stress. Their progress in treating RP mice using such vectors will be presented.

Simulating quantum mechanics on classical computers appears at first to require exponential computational resources, yet at the same time rapid progress is being made in accurate simulations of the quantum properties of realistic materials. How is this discrepancy resolved?

Topology, the "rubber sheet geometry", studies properties that do not change when objects are pulled and stretched. Accepting somewhat fuzzy input, it is the part of mathematics typically applied when qualitative conclusions are reached. However, it has a quantitative aspect important in understanding singularities, and potentially, high-dimensional noisy data and aspects of large-scale geometry of networks. Prof. Weinberger will discuss a variety of phenomena that arise or are illuminated by tracking of the complexity of geometric constructions.

Since at least the time when it was understood that the circumference of a circle is pi multiplied by its diameter, the applications of mathematics have raced on far ahead of the foundations of the subject itself. By considering a variety of examples, principally from the 19th century, we will explore the tension between mathematics and its applications, and reasons why it remains a valuable and rewarding occupation to develop the necessary framework for existing and “well understood” theories.

People spend hours a day interacting in online settings, ranging from social media sites to a broad range of digital communities designed for work, education and entertainment. Such systems are generally intended to elicit particular activities or forms of engagement, yet we have relatively little understanding of the resulting behaviors or of how system design may contribute to those behaviors. This talk will discuss work that aims to develop models of human behavior in online settings, both to inform system design but also to address fundamental questions in the social sciences.

Stochastic optical reconstruction microscopy (STORM), breaks the diffraction limit on light microscopy by using selective activation of photo-switchable fluorescent probes to temporally separate the spatially overlapping images of individual molecules. This approach has allowed multicolor and 3-D imaging of living cells with nanometer-scale resolution, enabling discoveries of novel sub-cellular structures. In this talk, Prof. Zhuang will discuss her group's development of STORM and its biological applications.

The Bonini laboratory focuses on applying the extraordinary power of a very simple model organism — the fruit fly Drosophila — to the complex problem of human neurodegenerative disease.