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.

Research Team

Research Areas

• Mechanisms of physiological metabolic reprogramming
• Roles of cellular metabolism in oocyte development
• Coordination of nutrition with metabolic requirements of oogenesis
• Inter-organ communication in coordination of cellular metabolism with animal physiology

Ongoing Research Projects

2023-2027 ERC Starting: The impact of germline metabolic reprogramming on reproduction and physiology. Coordinator: Zita Carvalho-Santos. Funding Agency: European Commission.

2020-2023 Metabolic reprogramming, dietary nutrients and food cravings in ovary aging. Co-Coordinator: Zita Carvalho-Santos. Funding Agency: Global Consortium for Reproductive Longevity and Equality (GCRLE).

Awards

2022 Outstanding poster award in the FASEB Reproductive Aging Meeting, Las Palmas, USA.

2020 Inaugural scholar of the Global Consortium for Reproductive Longevity and Equality (GCRLE) through the Buck Institute for Research on Aging, USA.

2020 Best Recorded Talk in Annual Portuguese Drosophila Meeting, Virtual. How does cellular metabolic reprogramming control sugar appetite?

Selected Publications

Li H, Janssens J, De Waegeneer M, Kolluru SS, Davie K, Gardeux V, Saelens W, David F, Brbić M, Leskovec J, McLaughlin CN, Xie Q, Jones RC, Brueckner K, Shim J, Tattikota SG, Schnorrer F, Rust K, Nystul TG, Carvalho-Santos Z, Ribeiro C, Pal S, Przytycka TM, Allen AM, Goodwin SF, Berry CW, Fuller MT, White-Cooper H, Matunis EL, DiNardo S, Galenza A, O’Brien LE, Dow JAT, Jasper H, Oliver B, Perrimon N, Deplancke B, Quake SR, Luo L, Aerts S, FCA Consortium. Fly Cell Atlas: a single-cell transcriptomic atlas of the adult fruit fly. Science. 2022 Mar 4;375(6584):eabk2432.

Carvalho-Santos Z†, Cardoso-Figueiredo R, Elias AP, Tastekin I, Baltazar C, Ribeiro C†. Cellular metabolic reprogramming controls sugar appetite in Drosophila. Nat Metab. 2020 Sep;2(9):958-973.

Henriques SF, Dhakan DB, Serra L, Francisco AP, Carvalho-Santos Z, Baltazar C, Elias AP, Anjos M, Zhang T, Maddocks ODK, Ribeiro C. Metabolic cross-feeding in imbalanced diets allows gut microbes to improve reproduction and alter host behaviour. Nat Commun. 2020 Aug 25;11(1):4236.

Ito D, Zitouni S, Jana SC, Duarte P, Surkont J, Carvalho-Santos Z, Pereira-Leal JB, Ferreira MG, Bettencourt-Dias M. Pericentrin-mediated SAS-6 recruitment promotes centriole assembly. Elife. 2019 Jun 11;8:e41418.

Carvalho-Santos Z, Ribeiro C. Gonadal ecdysone titers are modulated by protein availability but do not impact protein appetite. J Insect Physiol. 2017 Aug 24.

Leitão-Gonçalves R*, Carvalho-Santos Z*, Francisco AP*, Fioreze GT, Anjos M, Baltazar C, Elias AP, Itskov PM, Piper MDW, Ribeiro C. Commensal bacteria and essential amino acids control food choice behavior and reproduction. 2017. PLoS Biol 15(4): e2000862.

Carvalho-Santos Z*†, Pedro Machado P*, Alvarez-Martins I, Gouveia SM, Jana SC, Duarte P, Amado T, Branco P, Freitas MC, Silva ST, Antony C, Bandeiras TM, Bettencourt-Dias M†. BLD10/CEP135 is a microtubule-associated protein that controls the formation of the flagellum central microtubule pair. Dev Cell. 2012 Aug 14;23(2):412-24.

Carvalho-Santos Z†, Azimzadeh J, Pereira-Leal JB, Bettencourt-Dias M†. Origin and Evolution of Centrioles and Associated Structures. Journal of Cell Biology. 2011 Jul 25;194(2):165-75.

Carvalho-Santos Z, Machado P, Branco P, Rodrigues-Martins A, Pereira-Leal JB, Bettencourt-Dias M. Stepwise Evolution of Centriole Assembly Mechanisms. Journal of Cell Science. 2010 May 1;123(Pt 9):1414-26.

Bettencourt-Dias M, Carvalho-Santos Z. Double life of centrioles: CP110 in the spotlight. Trends in Cell Biology. 2008 Jan;18(1):8-11.

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