Goh Ket Yin earned a BSc at UCSI University, Malaysia, and is MSc in Medical Biosciences from University of Bath, United Kingdom. She has solid training in cell culture and transfection techniques, western blots and immunohistochemistry. She joins to assist in animal care and handling, mice genotyping and tissue harvest.
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The Sunday edition of the The Straits Times publishes today an interview with Carlos Ibanez highlighting the discovery of ALK7 link to fat deposition in obesity (reported in our paper published last week in eLife). Also newspapers MyPaper and Lianhe Zaobao carry stories (in Chinese) on the ALK7 discovery. In our latest paper, we report that the sensitivity of fat cells to signals that increase the breakdown of fat is linked to the receptor ALK7. The discovery, which is published today in eLife, suggests that ALK7 is an interesting target for future strategies to treat obesity. The ALK7 receptor is predominantly found in fat cells and tissues involved in controlling the metabolism. Intriguingly, mice with a mutation in ALK7 accumulate less fat than mice with a functional version of the protein. Until now, it has not been known why. We created mice whose fat cells lack ALK7, but whose other cells all produce ALK7 as normal. We found that fat cells lacking the ALK7 receptor are more sensitive to adrenaline and noradrenaline signals, a finding that can explain why they accumulate less fat even though the mice were on a high-fat diet. Adrenaline and noradrenaline are central players in metabolism. These hormones trigger the burst of energy and increase in heart rate and blood pressure that are needed for the “fight-or-flight” response. The hormones normally stimulate the breakdown of fat, but when nutrients are plentiful, fat cells become resistant to this signal and instead store fat. This mechanism evolved to facilitate energy storage during times of abundant food supply, enhancing survival upon starvation. In the industrialized world where food is constantly accessible, this resistance can cause an unhealthy increase in body fat and result in obesity. We then investigated if it is possible to prevent obesity by blocking ALK7. At present, there are no known ALK7 inhibitors, but we solved this by generating mice with a special mutation in ALK7 which renders it sensitive to inhibition by a chemical substance. This made it possible for us to block the receptor at any time in an otherwise normal adult animal. – Using this approach, we could get these mice to be leaner on a high fat diet simply by administration of the chemical. This suggests that acute inhibition of the ALK7 receptor can prevent obesity in adult animals, says Tingqing Guo, first author of the study. We have also showed that the ALK7 receptor works in a similar way in human fat cells as it does in mice. – Overall, these results suggest that blockade of the ALK7 receptor could represent a novel strategy to combat human obesity, says Carlos Ibanez, principal investigator of the study. The work was supported by grants from the European Research Council, Swedish Research Council, Strategic Research Program in Diabetes of Karolinska Institutet, Swedish Cancer Society, Knut and Alice Wallenberg Foundation, the National University of Singapore and the National Medical Research Council of Singapore. eLife is a peer-reviewed open-access scientific journal established at the end of 2012 by Nobel Prize Winner Randy Schekman, with support from the Howard Hughes Medical Institute, Max Planck Society and Wellcome Trust. The paper is freely accessible and can be found HERE. The Academic Research Fund of the Ministry of Education of Singapore has awarded a Tier2 research grant to Carlos Ibanez Lab to support work on activation and signal decoding mechanisms of neuronal death receptors, including p75NTR. A Research Assistant is currently being recruited to our NUS laboratory. The successful candidate will be a dynamic, service-minded person, with a solid research background in molecular biology, tissue culture, histological techniques and/or mouse genetics methods. He/she will have a strong presence in the laboratory by assisting the group by with experimental lab routines, including maintenance of mouse colonies, genotyping, molecular biology and histology, as well as conducting research together with other lab members or independently. Work at the laboratory focuses on understanding the functions and signaling mechanisms of neuronal growth factors and their receptors in neural development, injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolism. Applications including CV and names plus email addresses of three referees should be sent by email before September 5 to Prof. Carlos Ibanez The National Medical Research Council (NMRC) of Singapore has awarded two research grants to Carlos Ibanez Lab to support work on i) p75 neurotrophin receptor in nervous system physiology and neurodegeneration, and ii) ALK7 signaling in metabolic regulation, respectively. The latter is in collaboration with A/Prof. Sue-Anne Toh from NUS Department of Medicine. Yong Shan May has a BSc from the University of Malaya and will be defending her PhD thesis at NUS next year with title “ApoE isoform-specific modulation of NMDA receptor signalling pathway during ageing”. She has extensive expertise in experimental neuroscience including neuron isolation, immunohistochemistry and behavioural studies. Shan May joins our group to help with mouse breeding and genotyping, as well as immunohistochemical analyses of neurons in culture and tissue sections. Diabetologia has now published online our latest paper describing differential actions of activins A and B and Smad proteins 2 and 3 on the regulation of insulin secretion by pancreatic beta cells (Wu et al., 2013). Glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells is regulated by paracrine factors whose identity and mechanisms of action are incompletely understood. Activins are expressed in pancreatic islets and have been implicated in the regulation of GSIS. Activins A and B signal through a common set of intracellular components, but it is unclear whether they display similar or distinct functions in glucose homeostasis. Glucose homeostatic responses were examined in mice lacking activin B and in pancreatic islets derived from these mutants. The ability of activins A and B to regulate downstream signalling, ATP production and GSIS in islets and in beta-cells was compared. Mice lacking activin-B displayed elevated serum insulin levels and glucose-stimulated insulin release. Injection of a soluble activin B antagonist phenocopied these changes in wild type mice. Isolated pancreatic islets from mutant mice showed enhanced GSIS which could be rescued by exogenous activin B. Activin B negatively regulated GSIS and ATP production in wild type islets, while activin-A displayed opposite effects. The downstream mediator Smad3 responded preferentially to activin B in pancreatic islets and beta-cells, while Smad2 showed preference for activin A, indicating distinct signalling effects of the two activins. In line with this, overexpression of Smad3, but not Smad2, decreased GSIS in pancreatic islets. These results reveal a tug-of-war between activin ligands in the regulation of insulin secretion by beta-cells and suggest that manipulation of activin signalling could be a useful strategy for the control of glucose homeostasis in diabetes and metabolic disease. Read the full article HERE. A Research Assistant is currently being recruited to our NUS laboratory. The successful candidate will be a dynamic, service-minded person, with a solid research background in molecular biology, tissue culture, histological techniques and/or mouse genetics methods. He/she will have a strong presence in the laboratory by assisting the group by with experimental lab routines, including maintenance of mouse colonies, genotyping, molecular biology and cell culture experiments, as well as conducting research together with other lab members or independently. Work at the laboratory focuses on understanding the functions and signaling mechanisms of neuronal growth factors and their receptors in neural development, injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolism. Applications including CV and names plus email addresses of three referees should be sent by email before October 15 to Prof. Carlos Ibanez Eddy Goh obtained a PhD in Biochemistry at University College London, UK, under the supervision of Prof. Ivan Gout for his work on the nuclear functions of ribosomal S6 kinases. He did postdoctoral studies at the University of Dundee, Scotland, under the direction of Prof. Philip Cohen. Here Eddy studied mechanisms of regulation of E3 ligases in innate immunity. At our NUS group, he will investigate the mechanisms by which p75ntr couples to the NFkB pathway and devise novel mechanism-based approaches to modulate p75 signaling with small molecules. |
RhoGDI interaction to p75NTR |
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