Genética y Fisiología Molecular Versión en español

Subject
Hypoxia (low oxygen levels) is a common condition in a wide array of human pathologies, including cáncer, heart attack, stroke and diabetes, among others. Both under physiological or pathological conditions, animal cells modify their expression profile, tending to compensate oxygen shortage to madiate adaptation to this situation. In our lab we intend to define the mechanisms by which animal cells adapt to hipoxia. We are mainly interested in metabolic changes that occur in hipoxia, as well as in the activation of a process called autphagy. During autophagy cells digest part of their own cytoplasm to obtain nutrients required for survival. Autophagy is enhanced in situations where nutrients are scarse, such as under starvation or hipoxia.

Approach
Our lab utilizes the fruit fly Drosophila melanogaster as a model system, to study the molecular mechanisms that mediate adaptation to stress conditions. We are mostly interested on the interaction between such mechanisms and the signal transduction pathways involved in fly development.

Drosophila melanogaster has several experimental advantages for genetic experiments in vivo. On this basis, Drosophila has been intensively utilized over the last century for biological studies in developmental biology, genetics and physiology, among others. Drosophila, human beings, as well as all all other animals, utilize common cellular and molecular mechanism to adapt to hypoxia or to trigger autophagy. Thus, our work in Drosophila may have potential implications in understanding molecular mechanisms that underlay human pathologies.

Advances

We have found that the activation of autophagy by hypoxia or by starvation share common molecular mechanisms, and depend on the same set of genes. Moreover, we have found that autophagy is absolutely necessary for Drosophila larvae to adapt to hypoxia. We have identified a novel gene, which we have called Zonda, that is an essential regulator of both autophagy and the hypoxic response. In fact we discovered that Zonda is a more general regulator of vesicle trafficking, and has proved to be essential for the process of exocytosis. Detailed studies currently being carried out in our lab are aimed at defining the precise mechanisms by which Zonda participates in autophagy, exocytosis and the response to hypoxia.