24小时热门版块排行榜

返回列表

mjdee

新虫 (初入文坛)

应助: 0 (幼儿园)
金币: 47
帖子: 43
在线: 5.6小时
虫号: 3069645
注册: 2014-03-19
专业: 运动生理学

mTOR by AXIN

the research environment.
university of copenhagen, department of nutrition, exercise and sports (nexs) is currently ranked #1 on shanghai ranking among academic exercise and sports institutions worldwide.
https://nexs.ku.dk/english/

within nexs, the august krogh section of molecular physiology′s research output is a major contributor to this success, being the most productive in terms of scientific productivity, impact-metrics and funding-acquisition.
https://nexs.ku.dk/english/research/molecular-physiology/

in the section of molecular physiology, associate professor thomas e. jensen (tej) is the youngest of four 4 permanently employed pis, the others being professors erik a. richter, bente kiens and jørgen wojtaszewski, all well-recognized capacities within human molecular exercise metabolism research. in total, the section comprises at any given time an international mix of 30-40 phds, post docs, visiting scientists, and 4 shared lab technicians + 5-10 master students. tej heads one of 3 research groups within the section “muscle growth and metabolism” focusing on the study of signal transduction mechanisms in healthy and unhealthy skeletal muscle in models ranging from cell culture to mice to human biopsies.
his group currently comprises 4 post doc and 2 phd students. tej has supervised two csc phd students previously, both of which successfully completed their projects. references from former csc students can be provided upon request.

the project in brief.
phosphorylation mediated by kinases is a classical means of signal transduction. the ubiquitously expressed kinases amp-activated protein kinase (ampk) and mechanistic target of rapamycin (mtor) orchestrate the transition between cellular anabolism and catabolism. in skeletal muscle, these kinases have been linked to physiological adaptations to exercise as well as disease states and ageing 1╟4. a deeper understanding of ampk/mtor regulation may therefore inform new molecular targets to prevent or treat disease in skeletal muscle or elsewhere.
the scaffold protein axin1 was proposed to regulate lysosomal surface recruitment of mtorc1, and ampk activity in cytosol, on lysosomes and on mitochondria. its absence in muscle would ╟ based on the original paper 5 - be predicted to block ampk activation by exercise and various other ampk-stimuli, and to increase resting mtorc1 activity. my group generated the first inducible muscle-specific axin1 ko mice but observed surprisingly subtle effects on mtorc1 and ampk activation and normal metabolic regulation 6. the mild phenotype in axin1 ko muscle may be due to compensation by the remaining axin2 isoform, reported later to be functionally redundant 7.
to follow up, i generated a muscle-specific inducible muscle-specific axin1/2 double knockout mouse model. the characterization of this model will be the low-risk backbone of this project. in addition, as a more high-risk add-on, this phd project will help develop and test an innovative subcellular compartment-specific kinase activity reporter system in adult mice in close collaboration with senior post docs in tej′s group. this will likely entail a change of environment in a collaborator-lab to train in packaging of kinase-reporters into muscle-targeted adeno-associated virus.

references
1. jensen, t. e., wojtaszewski, j. f. p. & richter, e. a. amp-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient? acta physiol. 196, 155╟174 (2009).
2. knudsen, j. r. et al. growth factor-dependent and -independent activation of mtorc2. trends in endocrinology and metabolism vol. 31 13╟24 (2020).
3. ogasawara, r., jensen, t. e., goodman, c. a. & hornberger, t. a. resistance exercise-induced hypertrophy: a potential role for rapamycin-insensitive mtor. exerc. sport sci. rev. 47, 188╟194 (2019).
4. gonzález, a., hall, m. n., lin, s. c. & hardie, d. g. ampk and tor: the yin and yang of cellular nutrient sensing and growth control. cell metab. 31, 472╟492 (2020).
5. zhang, c. s. et al. the lysosomal v-atpase-ragulator complex is a common activator for ampk and mtorc1, acting as a switch between catabolism and anabolism. cell metab. 20, 526╟540 (2014).
6. li, j. et al. axin1 knockout does not alter ampk/mtorc1 regulation and glucose metabolism in mouse skeletal muscle. j. physiol. (2021) doi:10.1113/jp281187.
7. zong, y. et al. hierarchical activation of compartmentalized pools of ampk depends on severity of nutrient or energy stress. cell res. 29, 460╟473 (2019).

your profile.
the candidate should have a degree in physiology, biochemistry, medicine or similar, preferably with a strong background in and understanding of molecular cell biology, biochemistry and metabolism. prior laboratory work experience will be considered an advantage, in particular experience with biochemical analyses, microscopy and mouse work. english is the main language of communication at the department and internationally in science and excellent written and oral english language skills will thus be an explicit selection criterion.

outside science.
copenhagen is steadily ranked among the safest and most livable cities in the world (#1 in safe city index 2021)
https://edition.cnn.com/travel/article/the-worlds-safest-city-2021-revealed/index.html
the neighborhood nørrebro close to campus was recently ranked coolest on earth by time out magazine.
https://secretkobenhavn.com/norrebro-coolest-neighborhood/
on november 1st 2021, 76% of the danish population is covid19-vaccinated and society is fully open.
https://ourworldindata.org/covid-vaccinations?country=owid_wrl
apart from the many sights in copenhagen and denmark, denmark sits conveniently on top of western europe and within a few hours travel of major cultural and historical cities including berlin, paris, london and rome.

if interested in joining us, please send your cv and1 page motivation to email address: tejensen@nexs.ku.dk