Zita Carvalho-Santos Lab

Organismal Metabolic Physiology

Metabolic processes are at the core of all cellular functions. Cells can undergo metabolic reprogramming, a process by which metabolism is rewired as a way of acquiring new functions. The most well-described example is the rewiring of metabolism observed in tumor cells. However, although most intensively studied in pathological conditions, metabolic reprogramming also occurs in physiological settings, being best appreciated in the context of development of multicellular organisms which are composed by various cell types with different metabolic needs.

A challenge faced by those organisms is that tissue-specific metabolic requirements need to be coordinated at the whole-organism level. To achieve this task, animals use an extensive network of inter-organ communication that regulate tissues’ functions and allow the organism to maintain homeostasis. Furthermore, changes in the environment, induce a coordinated adjustment of multi-organ metabolic statuses. Although inter-organ communication is at the core of animal physiology and behavior, we are still far from understanding the molecular mechanisms mediating it and the factors that regulate it.

How animals satisfy the metabolic needs of different tissues and, in turn, how cell-specific metabolic programs modulate animal physiology remains largely unexplored. In our lab, we aim to uncover novel mechanisms allowing organisms to integrate cell-specific metabolic programs with internal and external factors to mount cell-specific strategies which expand to the whole-animal, impacting physiology, with a focus on reproduction.

Female fertility has emerged as a highly relevant paradigm to study the integration of inter-organ communication with cell metabolism and dietary nutrients. Oogenesis is regulated by the concerted action of multiple organs, modulated by secreted factors such as hormones, and intricately linked to animal development. It is a metabolically expensive process that requires the provision of a balanced diet. Several factors have been shown to impact female fertility including female age, dietary nutrient availability and colonization by gut microbes, but if and how these factors impact metabolic processes in the germline is not known. Because of the complex nature of this regulatory network controlling female fertility, tackling this question requires a systems biology approach combined with a highly tractable model system, such as Drosophila.