Metabolic processes are at the core of all cellular functions. Unraveling the mechanisms that enable animals to address the metabolic demands of various tissues, and understanding how cell-specific metabolic programs impact overall animal physiology, is a fundamental question to understand all biological systems.

Cells can undergo processes of metabolic reprogramming, a phenomenon 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. Furthermore metabolic adjustments can occur as a response to external stimuli such as a change in availability of dietary nutrients.

A challenge faced by multicellular organisms is that tissue-specific metabolic requirements need to be coordinated at the whole-organism level. To achieve this task, animals use an extensive inter-organ communication network that regulate tissues’ functions and allow the organism to maintain homeostasis.

How animals satisfy the metabolic needs of different tissues and, in turn, how cell-specific metabolic programs modulate animal physiology remains largely unexplored. Our laboratory’s primary goal is to understand the interaction between nutrition, cellular metabolism, and animal physiology. Our research aims at revealing the mechanisms that allow animals to integrate dietary nutrient availability with cell-specific metabolic processes, thereby influencing cellular functions that resonate throughout the entire animal. On a different perspective, we are also interested in understanding how organ functional statuses impinge on animal physiology to regulate feeding behavior, directing nutrient appetites to meet specific metabolic needs.

Given the complexity of this question, which spans diverse scientific domains, we use a systems biology approach combined with a highly tractable model system—the fruit fly—to tackle this question. Our previous findings established an innovative framework which we will now use for:

• studying the molecular mechanisms governing the transcriptional implementation and adaptability of metabolic programs

• exploring the functions of specific metabolic pathways and metabolites in sub-cellular, cellular and tissue functions

• identifying the intricate molecular mechanisms linking cellular metabolism with inter-organ communication and its role in regulating animal physiology.

Given the high conservation of metabolism across organisms, our results will carry broad implications, both at the fundamental biological level (for exp. how metabolic plasticity drives adaptation to environmental changes) as well as at the level of disease states (for exp. how tissue-specific metabolic alterations can lead to disorders).

2023/2027: The impact of germline metabolic reprogramming on reproduction and physiology. Coordinator: Zita Carvalho-Santos. Funding Agency: European Commission. Reference: ERC-101043068-SWEETEGGS.

2023/2025: Sub-cellular Metabolic Compartmentalization during Oocyte Development. Coordinator: Zita Carvalho-Santos. Funding Agency: Chan Zuckerberg Initiative. Reference: CZI – MEASURING METABOLISM ACROSS SCALES.

2023/2024: The role of healthy cells on the elimination of premalignant cells. Coordinator: Catarina Brás-Pereira. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/BIA-CEL/3594/2020.

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.

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.

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?