Career Pathways Collection

The transition from senior postdoc to early-stage investigator is a pivotal step in the careers of academic scientists. In this series, early-stage investigators reflect on their labs’ first publications and the journeys that led them there.

In this instalment of Career pathways, we hear from Anja Zeigerer and Myriam Aouadi about how the support of institutions, labs and families can galvanize scientists’ passion and productivity.

In this instalment of Career pathways, Jing Fan and Edward A. Phelps reflect on fostering their newly formed research programs in the face of challenges both familiar and new.

Learning to balance work, family, optimism and setbacks is a process for all early-career investigators. Stephanie Correa and Leng Han share their stories in this instalment of Career pathways.

In this instalment of Career pathways, Kivanç Birsoy and Sarah Lessard recount their roads to scientific research and reflect on how each step in their training prepared them for life as a group leader.

In this instalment of Career pathways, James White and Wenjing Du reflect on the importance of recruiting the right people, staying excited and making work and home life coexist.

In this instalment of Career pathways, Sa Kan Yoo and Youssef Idaghdour share their research journeys across continents and reflect on their experiences of setting up a new lab and finding a research focus.

Maria Ermolaeva and Liron Boyman share their scientific journeys in this instalment of Career pathways and highlight the value of mentors and collaborators, and the importance of following your research interests.

Evanna Mills and Edward Chouchani share the experience of their successful mentor–mentee relationship and talk about the challenges of starting a new lab — both from a recent perspective and five years on.

In our tenth instalment of Career pathways, Jin Zhang and Christiane Wrann reflect on their journeys to becoming PIs and the importance of having a vision for your research, finding the right team, and sharing the joy of science through the training of students.

In this instalment of Career pathways, we hear from Gerta Hoxhaj and Ed Reznik about how they followed their passion for science, the value of collaborations and mentors, asking big questions and how to think differently about metabolism.

Bilal Sheikh and Yuxiong Feng share their scientific journey and how it has taken them around the world and given them freedom to pursue their curiosity and own ideas. They share the passion that drives their research and highlight the importance of building a strong, collaborative and complementary team.

Following one’s passion and curiosity are major drivers for a successful career in science, and finding the right mentors and collaborators is essential in this journey. In the thirteenth part of our Career pathways series, Alexis Jourdain and Feilong Wang share their experience.

Angelika Rambold and Santiago Vernia reflect on how a very early interest in science has shaped their career, their research interests and their mentoring style.

In this new instalment of our Career Pathways series, Marina García-Macia and Fei Yin highlight the impact and joys of building a team and share with us key milestones that have shaped their careers so far, including the importance of making the most of every situation, finding the right mentors, and pursuing the questions that they are passionate about.

In this instalment of our Career Pathways series, Cholsoon Jang and Min-Dian Li share how curiosity from a very early age has driven their scientific journeys.

Leah Gates and Ben Weaver reflect on how overcoming different hurdles and dealing with unexpected events has ultimately shaped their careers. They also emphasize the importance of relying on a strong support network.

Glutamine is a major fuel for proliferating cells. Here the authors show that reduced dependence on exogenous glutamine is a generalizable feature of self-renewing pluripotent stem cells that can be exploited to select for mouse and human pluripotent stem cells with high self-renewal potential.

Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.

Proinflammatory activation of liver macrophages and their secretion of proinflammatory cytokines have been linked to obesity. Here Morgantini et al. report a mechanism through which liver macrophages can impair liver metabolism and promote insulin resistance in obesity in the absence of an overt proinflammatory phenotype, through secretion of non-inflammatory factors such as IGFBP7.

Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.

Macrophages engage in a sequence of dynamic functional changes during immune responses. Here the authors elucidate a two-stage remodelling of the tricarboxylic acid cycle during this process, which is driven by regulation of the pyruvate dehydrogenase and the oxoglutarate dehydrogenase complexes, and causes transient accumulation of immunoregulatory metabolites.

Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.

The ventromedial nucleus of the hypothalamus is known to maintain energy homeostasis by controlling locomotor activity and thermogenesis. Here van Veen and Kammel et al. identified heterogeneous neuronal populations with sexually dimorphic gene expression and functions by using single-cell RNA analysis.

The conventional view holds that hypoxia confers drug resistance. In contrast, here the authors use a multilayer ‘omics data approach to characterize the molecular features associated with tumour hypoxia and identify molecular alterations that correlate with both drug-resistant and drug-sensitive responses to approved drugs.

The muscular and organismal response to exercise training is reduced in animal models associated with chronic hyperglycaemia, thus suggesting that chronic hyperglycaemia inhibits aerobic adaptation to exercise.

Bayraktar et al. construct a metabolic coessentiality network to cluster metabolic genes into networks from perturbation datasets derived from 558 cancer cell lines. They identify C12orf49 as an essential component of SREBP processing and cholesterol sensing in mammalian cells.

The immune system is known to play an important role in regenerative processes. Here, Baht and colleagues identify Metrnl, a myokine/cytokine expressed in macrophages, as mediator of muscle regeneration. Metrnl promotes macrophage IGF-1 production that, in turn, activates satellite cells.

Li et al. report a non-metabolic role of NADPH as an inhibitor of HDAC3, thus linking NADPH levels with the epigenetic state of a cell.

The Drosophila white mutant has been used extensively for genetics studies. Sasaki et al. show a metabolic role of white, which is found to regulate intestinal stem cell proliferation during ageing through folate metabolism.

Longitudinal changes in the serum metabolome and transcriptional changes in immune cells are mapped in children from two different ethnic groups in West Africa who were exposed to seasonal malaria, thereby identifying an immunosuppressive role of endogenous steroids that are induced by P. falciparum infection.

Metformin holds the potential to extend healthy lifespan in aged, insulin-resistant individuals. Using C. elegans, Espada et al. uncover a deleterious metabolic response to metformin treatment in aged worms with unaltered insulin signalling.

Here the authors provide a regulatory framework for the cardiac mitochondrial ATP synthase, which is shown to be dependent on cellular activity; levels of Ca²⁺, ADP and NADH; and the potential of the inner mitochondrial membrane.

UCP1 is exclusively expressed in brown and beige adipocytes, where it drives thermogenesis through futile substrate cycling. Mills et al. identify a endocrine pathway mediated by the UCP1 catabolic circuit that antagonizes liver inflammation by lowering the concentration of succinate in the liver extracellular fluid.

By using an integrated omics approach, a landscape of metabolic remodelling of early-stage mouse embryogenesis is reconstructed, identifying key metabolites for epigenetic reprogramming.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

NADPH exists in separate cellular pools within the cytosol and mitochondria. Tran et al. find that mitochondrial NADPH is essential to enable proline biosynthesis during cell growth.

Using whole-exome sequencing data, Gorelick et al. identify lineage-specific somatic mutations in mitochondrial DNA that affect cancer progression and patient prognosis.

Bondareva and Rodríguez-Aguilera et al. use scRNA-seq to analyze transcriptomes of 375,000 endothelial cells from seven organs in male mice at various stages of obesity to identify organ-specific vulnerabilities.

Zhao et al. report a role for glutamine synthetase in regulating cell proliferation that does not require the catalytic activity of the enzyme.

Previous work using chemical inhibitors has reported the need for the mitochondrial pyruvate carrier for the classical activation of macrophages. In this study, Ran, Zhang et al. use a genetic approach to show that LPS-stimulated macrophage activation does not require the import of pyruvate into mitochondria.

In this study, Skinner, Blanco-Fernández et al. show that uridine can be salvaged through the non-oxidative branch of the pentose phosphate pathway to feed glycolysis in conditions of glucose scarcity.

The key regulator of lysosomal biogenesis, Tfeb, is shown to directly induce Irg1 transcription and mitochondrial itaconate production to restrain bacterial growth in macrophages.

Paterson and Yu et al. demonstrate that loss of the RNA alternative splicing factor RBFOX2 in the liver during a lipogenic diet leads to dysregulation of liver lipid and cholesterol homeostasis through a specific alternative splicing programme, which includes a splice switch of the high-density lipoprotein receptor gene Scarb1.

Mi, Qi et al. identify a mechanism through which defective oxidative phosphorylation in astrocytes deregulates astroglial lipid homeostasis and subsequently impacts neurons and microglial cells, thus triggering neuronal damage and microglial reactivity.

In this study, Morant-Ferrando, Jiménez-Blasco et al. show that fatty acid oxidation in astrocytes is necessary to maintain a specific configuration of the electron transport chain, which enables controlled production of reactive oxygen species that fine-tune neuron–glia metabolic coupling and support cognitive function.

In this study, Park, Haley, Le, Jung et al. perform a detailed characterization in vivo of metabolic flux distribution during thermogenesis and uncover brown fat nutrient fluxes and unexpected inter-organ metabolic crosstalk and glutamine utilization.

Time-restricted feeding in the resting period is a potent dietary regimen to enhance running endurance in mice, by synchronizing rhythms of perilipin-5 in muscle tissues through involvement of the circadian clock.

Wei et al. show that proteolytic cleavage of fatty acid synthase (FASN) upon stress contributes to stress resolution. This role in stress resolution of the resulting C-terminal fragment of FASN is independent of its canonical function in fatty acid synthesis.

Gates et al. show that histone butyrylation and propionylation in the intestinal epithelium are regulated by the gut microbiota and histone butyrylation is associated with gene regulatory programmes.