Integrated Calendar

Obesity is a complex disease with its roots in the physiology of various brain circuits. Although much progress has been made in understanding the disease, the most fundamental question remains unanswered – why do we overeat? As Clifford Saper (Harvard) points out, “if feeding were controlled solely by homeostatic mechanisms, most of us would be at our ideal body weight, and people would consider feeding like breathing or elimination, a necessary but unexciting part of existence”. Clearly this is not the case; hedonic eating has come increasing under the spotlight in recent years as a main driver of obesity. As food becomes more and more rewarding, could overeating be driven by a pathological search for reward? In my talk I will demonstrate that chronic diet of highly-palatable food changes the physiology of the reward system and that mice that gained the most weight differ from those that gained the least weight in the physiology of two regions of the reward system – the nucleus accumbens and the ventral pallidum. Furthermore, I will show that long term plasticity in the ventral pallidum may be an innate marker for the predisposition to overeat palatable food.

I will present trans-Tango, a new technique for anterograde transsynaptic circuit tracing and manipulation that we have established in fruit flies. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell-surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners. Activation of the pathway culminates in expression of a reporter that can be visualized. Because our system is modular, it can be easily adapted to experiments in which the properties of specific circuits are modified and the functional consequences are analyzed. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the firstorder receptor neurons are not well characterized. We identified second-order neurons within the sweet and bitter circuits and revealed that they target brain areas involved in neuromodulation with similar but distinct projection patterns. I will also present experiments in which we use trans-Tango in functional analysis of the gustatory circuits. Using our studies in flies as proof of concept, we are currently establishing an equivalent technique for labeling circuits in vertebrate models, such as mice and zebrafish. These experiments establish trans-Tango as a flexible platform for comprehensive transsynaptic analysis of neural circuits.

ChronoLog is a new tool for computer-assisted chronological research. It allows its users to build models featuring chronological sequences (such as dynasties, stratigraphic sequences and historical periods) and synchronisms between the items of these sequences. Each item (reign of a king, archaeological stratum, historical period) can be provided with an exact or approximated start date, end date and duration. The software uses this information to compute the tightest possible estimates (expressed as ranges) for each date and duration. The tool also checks the validity of the model, and reports cases where the encoded data are contradictory. Such a tool is important as it allows users to examine large chronological models that are otherwise too difficult to study manually. The tool is used in an interactive way, allowing to immediately assess the impact of a given hypothesis on the overall chronological network. Users can thus check the impact of altered dates for a given king, or the addition of a new synchronism between two strata. They can also test hypotheses, in order to check, for example, if two kings were contemporaries. The software runs fast, allowing users to obtain instantaneous answers to the above-described queries. The presentation will feature a demo of ChronoLog and a case study.

The ability of pathogens to sense and respond to changes enables them to adapt and survive in hostile environments. In particular, microbes have developed a mechanism called quorum sensing, in which they produce, detect and respond to small, secreted molecules. One of the deadliest pathogens in humans is the parasite Plasmodium falciparum (Pf), the infectious agent of the malaria disease, accounting for the death of about half a million people annually. Here, we reveal that these parasites employ a quorum sensing-like mechanism to respond to their own density and coordinate their asexual growth during the blood stage of their life cycle. Namely, Pf parasites govern their own cell density by secreting active molecule(s). Using a combination of biochemical techniques, we chemically characterized the active fraction (autoinducer-like molecule) and revealed it to be a hydrophilic, positively charged molecule of a size ranging from 100Da to 4,000Da. Further purification using high-pressure liquid chromatography (HPLC) enabled the putative detection of two metabolites. Our finding suggests that malaria parasites signal each other to coordinate their asexual growth pattern is a previously unrecognized survival strategy. Identification and further investigation of the active secreted molecule can potentially lead to the development of anti-malaria drugs.