Ph.D. by Research at Universitas Padjadjaran : Role of Hippo Pathway Effectors in Aging

Information: This scholarship is funded by Universitas Padjadjaran - Indonesia

Subject Areas: Biomedical Sciences

Project Title: Elaborating Role of Hippo Pathway Effectors YAP and TAZ and their association with skeletal muscle ageing

Project Supervisor: dr. Ronny, M.Kes., AIFO., Ph.D

Project Description:

The United Nations Population Fund have predicted that by 2035, the number of people aged 60 or above in Indonesia will reach 15% or twice the level in 2010.1 Increasing population age have wide implications both economically and also in the healthcare sector. Old age is associated with significant comorbidities such as degenerative and cardiovascular diseases. Additionally, the loss in muscle mass further decreases their quality of life.2 Equipped with this knowledge, an intervention must be developed to deal with this looming problem. One well known intervention to improve the quality of life in the aging population is exercise.

Exercise is defined as a form of structured and regular physical activity3 and has been known to improve the aging process.4 Exercise exerts its effect through the regulation of metabolisms, inflammations, and the immune system. Several possible mediators of exercise effects are through myokines, autophagy, and the Hippo signalling pathway. Myokines are cytokines secreted by the skeletal muscle in association with exercises.5 Several myokines have already been identified with interleukin 6 being the first identified myokines which is implicated in the regulation of muscle hypertrophy.6 The Hippo pathway are also associated with organ size regulation. The effector of the pathway, Yes-associated protein (YAP) and its homologue transcriptional coactivator with PDZ-binding motif (TAZ) are implicated in increased muscle size.7,8 Autophagy is another important effector of the effects of exercise. Although at first seemed counterintuitive, autophagy helps maintain cellular homeostasis and in fact are associated with the prevention of aging.9 Therefore, these pathways involvement in muscular hypertrophy may reverse the loss of muscle mass associated with aging.

Several different types of exercise intensity have been characterized according to the lactate threshold. Our research team have established the lactate threshold model of exercise intensity in rats10 and have conducted preliminary studies exploring the association of different exercise intensity and processes associated with aging. Several processes that we have explored are the effects of different exercise intensity on autophagy in skeletal muscles11, cardiac muscle12,13, and hepatic tissues14. Using this data, we are trying to expand our research on aged mice to see whether these responses is modified by aging itself.

Other aspects that we’re also trying to explore is the regulation of absorption of different nutrients in old age. The common metabolic diseases such as dyslipidaemia and diabetes are highly associated with age. Several research have associated the degeneration of the gastrointestinal tracts with impaired nutrient absorption.15 In this project we are also planning to evaluate whether exercise can improve the effects whether through alterations in cellular signals in the gut or other pathways.

By understanding the pathways implicated in muscle size regulations and changes in the aging processes, several potential therapeutic avenues are revealed. Finding the optimal exercise intensity which provide the greatest benefit while minimizing the risk associated with exercise is essential. Additionally, by understanding the pathway involved in exercise that influences muscle size, we may also exploit and influence these pathways with exogenous substances or supplements and alter or prevent skeletal muscle aging.

1. This scholarship is open to candidates of any nationality;
2. Applicants should hold a minimum of Master's degree (or its equivalent) in Biomedical Sciences. However, other related discipline with relevant experience will be considered.;
3. Age limit: Applicants must be under 31 years old;
4. Minimum GPA of 3.5 (out of 4) or equivalent. Academic transcripts are required from every college you have attended for at least one academic year as a full-time student. Your transcripts should be uploaded as a scanned copy or PDF. Please ensure that the degree conferral date and the degree conferred is clearly visible on the document.
5. English Language Requirements:
6. You need to achieve the minimum scores shown for any of the English language tests below:

• Minimum overall score for International TOEFL (Paper-Based Test): 525 OR;
• Minimum overall score for International TOEFL (Internet-Based Test): 70 OR;
• Minimum overall score for International TOEFL (Computer-Based Test): 190 OR;
• Minimum overall score for International English Language Testing System (IELTS) Academic: 6.

1. Full cost of tuition fees at the Doctoral Program in Universitas Padjadjaran;
2. Monthly living allowance IDR 2.500.000 for 3 (three) years during the Doctoral Program;
3. 1 (one) time return airfare ticket to and from Jakarta Indonesia (from and to the candidate's nearest international airport);
4. Health insurance for 3 (three) years, during the Doctoral Program;
5. There will be additional funds available for research expenses for 3 (three) years during the doctoral program.

To apply, please complete and submit the following documents to international@unpad.ac.id, and address the email for your application as 'Padjadjaran Doctoral Scholarship – Ronny':

1. Degree certificates and transcripts;
2. Two letter of recommendations. Applicants are required to submit two letters of recommendation. These recommendations should be written by people who have supervised you in an academic, employment, or community service setting. Your recommendations should directly address your suitability for admission to a postgraduate program at Universitas Padjadjaran;
3. Statement of Purpose. Your statement should be typed, single-spaced and should be between two to three pages. Describe your reasons for applying to the proposed program, your preparation for this field of study, and explain why the position particularly matches your skills and experience, and how you choose to develop the project, which may aid the admissions committee in evaluating your motivation for postgraduate study.
4. 2-page Curriculum Vitae;
5. Certificate of Proficiency in English; and
6. Other supporting documents.

If you require any further information with regard to this, please contact international@unpad.ac.id.