לוח שנה משולב

Our work concerns the general problem of adaptive behavior in response to predatory threats, and of the neural mechanisms underlying a choice between strategies. Interacting predators and prey tightly regulate their motion, timing with precision when to hold, attack or escape. Motion cues are thus paramount in these interactions. Speed and (un)predictability have shaped the evolution of sensory and motor systems, the elucidation of which a great deal of research has been devoted. Much less attention has been paid to the role of motion as a social cue of threat or safety. We and others have found that prey animals use the movement of their neighbors to regulate their defensive responses. We have studied social regulation of freezing in rodents and found that rats use cessation of movement evoked sound, resulting from freezing, as a cue of danger. In addition, auto-conditioning, whereby rats learn the association between shock and their own freezing, during prior experience with shock, facilitates the use of freezing by others as an alarm cue. To further explore the social regulation of defensive responses we resorted to the use fruit flies as it easily allows testing of groups of varying sizes, the collection of large data sets and genetic access to individual neuronal types. We established that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices accompanied by lasting changes in the fly’s internal state, reflected in altered cardiac activity. Freezing in flies is also strongly modulated by the movement of surrounding neighbours. In contrast with rodents that use auditory cues, female flies use visual motion processed by visual projection neurons. Finally, I will discuss more preliminary findings suggesting that there are multiple states of freezing as measured by muscle activity in the fly legs. Having established the fly as a model to study freezing/fleeing decisions, we are in a great position to perform large scale integrative studies on the organization of defensive behaviours.
Short Bio
Marta Moita received her BSc degree in Biology at the University of Lisbon, in 1995. As part of Gulbenkian’s PhD programme in Biology and Medicine she developed her thesis work, on the encoding by place cells of threat conditioning under the supervision of Prof. Joseph Ledoux, at the New York University (1997-2002). In 2002, Marta Moita worked as a postdoctoral fellow in Dr. Tony Zador’s laboratory, at the Cold Spring Harbor Laboratory, to study the role of auditory cortex in sound discrimination. In 2004, she became a principal investigator, leading the Behavioral Neuroscience lab, at the Instituto Gulbenkian de Ciência. In 2008 her group joined the starting Champalimaud Neuroscience program. In 2018 and 2019 Marta Moita served as Deputy Director of Champalimaud Research. Her lab is primarily interested in understanding the mechanisms of behavior. To this end, the lab has focused on behaviors that are crucial for survival and present in a wide range of species, namely defensive behaviors triggered by external threats. Using a combination of state-of-the-art tools in Neuroscience (initially using rats and currently using fruit flies) and detailed quantitative descriptions of behavior, her lab aims to understand how contextual cues guide the selection between different defensive strategies and how the chosen defensive behavior and accompanying physiological responses are instantiated.
   

Neurodegenerative diseases are often clinically, genetically, and pathologically heterogeneous. The clinical impact of understanding heterogeneity is perhaps best observed in cancer, where subtype-specificity within diagnoses, prognoses, and treatments have had a critical impact on clinical decision making and patient outcomes. A better understanding of how mechanisms are related to or drive heterogeneity within diseases such as Amyotrophic Lateral Sclerosis (ALS), will have a direct impact on patient outcomes, with a conscious effort to move towards precision medicine and targeted therapeutics for patients, which are urgently needed. For this reason, neuroscientists and oncologists have long aspired to achieve an understanding of the mechanisms governing pathophysiology. Our interdisciplinary work integrates technologies across a wide range of fields to surpass the current barriers in understanding disease pathophysiology. This talk will highlight a series of optical and photoacoustic imaging tools as well as multi-omics analysis that have been developed and studied in Dr. Smith’s lab to address the urgent need for non-invasive cancer detection and the characterization of neurological disorders. Through this work, we aim to develop translational technologies and methodologies to better characterize, understand, and detect disease pathogenesis, beyond current capabilities.

DNA can be damaged by chemicals in our surroundings, and occurs at the nucleophilic sites on the strand. Of particular interest is alkylation at the O6-position of guanine, which goes on to cause G:C -> A:T mutations. These mutations cause genomic instability and are linked to the onset of colorectal cancer (CRC). Identifying the extent and diversity of O6-guanine alkylation informs us on the exposure cancer patients have undergone.
Here we have developed a mass spectrometry based approached to identify damaged DNA. The method is based on the DNA repair protein MGMT, which directly removes alkylation from O6-alkyl guanine. MGMT can be used to probe the type and extent of O6-alkylation.