Tracking the career development of scientists in low- and middle-income countries trained through TDR's research capacity strengthening programmes: Learning from monitoring and impact evaluation.

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The "brain drain" phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR's research capacity grant programmes made a difference on researchers' career development and on south-south collaborations, by strengthening and localizing research capacity in lower income regions, and also showed there is more that needs to be done. The factors involved, challenges and lessons learnt may help donors and policy makers improve their future interventions with regard to designing capacity strengthening programmes and setting funding priorities

Occupational area and gender of TDR respondents (in %) (percentages do not add up to 100% since respondents can work in more than one occupational area).

<p>Occupational area and gender of TDR respondents (in %) (percentages do not add up to 100% since respondents can work in more than one occupational area).</p

Tracking the career development of scientists in low- and middle-income countries trained through TDR’s research capacity strengthening programmes: Learning from monitoring and impact evaluation

<div><p>The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The “brain drain” phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR’s research capacity grant programmes made a difference on researchers’ career development and on south-south collaborations, by strengthening and localizing research capacity in lower income regions, and also showed there is more that needs to be done. The factors involved, challenges and lessons learnt may help donors and policy makers improve their future interventions with regard to designing capacity strengthening programmes and setting funding priorities.</p></div

Profile of the 77 TDR trainees who responded to the survey.

<p>(A) geographic distribution by WHO region (AFR for African region; AMR for region of the Americas, SEAR for South East Asia region, EMR for Eastern Mediterranean region and WPR for Western Pacific region); (B, C) gender distribution in total and by WHO region, respectively; (D) use of language in AFR; (E) employment status of trainees by function (E1), and by nature (E2 and E3).</p

TDR respondents by career stage (Frascati definition) [7, 8] and gender (in %).

<p>TDR respondents by career stage (Frascati definition) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006112#pntd.0006112.ref007" target="_blank">7</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006112#pntd.0006112.ref008" target="_blank">8</a>] and gender (in %).</p

Health research mentorship in low-income and middle-income countries: a global qualitative evidence synthesis of data from a crowdsourcing open call and scoping review

Introduction Research mentorship is critical for advancing science, but there are few practical strategies for cultivating mentorship in health research resource-limited settings. WHO/TDR Global commissioned a group to develop a practical guide on research mentorship. This global qualitative evidence synthesis included data from a crowdsourcing open call and scoping review to identify and propose strategies to enhance research mentorship in low/middle-income country (LMIC) institutions.Methods The crowdsourcing open call used methods recommended by WHO/TDR and solicited descriptions of strategies to enhance research mentorship in LMICs. The scoping review used the Cochrane Handbook and predefined the approach in a protocol. We extracted studies focused on enhancing health research mentorship in LMICs. Textual data describing research mentorship strategies from the open call and studies from the scoping review were coded into themes. The quality of evidence supporting themes was assessed using the Confidence in the Evidence from Reviews of Qualitative research approach.Results The open call solicited 46 practical strategies and the scoping review identified 77 studies. We identified the following strategies to enhance research mentorship: recognising mentorship as an institutional responsibility that should be provided and expected from all team members (8 strategies, 15 studies; moderate confidence); leveraging existing research and training resources to enhance research mentorship (15 strategies, 49 studies; moderate confidence); digital tools to match mentors and mentees and sustain mentorship relations over time (14 strategies, 11 studies; low confidence); nurturing a culture of generosity so that people who receive mentorship then become mentors to others (7 strategies, 7 studies; low confidence); peer mentorship defined as informal and formal support from one researcher to another who is at a similar career stage (16 strategies, 12 studies; low confidence).Interpretation Research mentorship is a collective institutional responsibility, and it can be strengthened in resource-limited institutions by leveraging already existing resources. The evidence from the crowdsourcing open call and scoping review informed a WHO/TDR practical guide. There is a need for more formal research mentorship programmes in LMIC institutions

Macromolecular condensation buffers intracellular water potential

Acknowledgements: The order of the second and corresponding authors is arbitrary and these authors can change the order of their respective names to suit their own interests. This work has been supported by the Medical Research Council, as part of United Kingdom Research and Innovation (MC_UP_1201/13 to E.D.; MC_UP_1201/4 to J.S.O. and MCMB MR/V028669/1 to J.E.C.), the Human Frontier Science Program (Career Development Award CDA00034/2017 to E.D.), a Versus Arthritis Senior Research Fellowship Award (20875 to Q.-J.M.) and an MRC project grant (MR/K019392/1 to Q.-J.M.), a Grifols ‘ALTA’ Alpha-1-Antitrypsin Laurell’s Training Award and an Alpha-1-Foundation (grant number 614939) to J.E.C., and by a Wellcome Trust Sir Henry Dale Fellowship (208790/Z/17/Z to R.S.E.). N.M.R. is supported by a Medical Research Council Clinician Scientist Fellowship (MR/S022023/1). L.K.K. and V.J.P.-H. are recipients of EMBO Postdoctoral fellowships (ALTF 876-2021 and ALTF 577-2018, respectively). K.E.M. is supported by the Wellcome Trust through a Sir Henry Wellcome Postdoctoral Fellowship (220480/Z/20/Z). P.M.M. and J.B. were supported by Volkswagen ‘Life’ grant number 96827 and the DFG Excellence Cluster Physics of Life. We thank H. Andreas for frog maintenance; C. Godlee and M. Kaksonen for the gift of unpublished S. cerevisiae yeast strains and initial discussion of yeast experiments about temperature; P. Tran for S. pombe yeast strains; L. Miller for help with yeast work; A. Bertolotti for the kind gift of SH-SY5Y cells; and C. Russo, F. Jülicher, M. Gonzalez-Gaitan, K. Kruse, L. Blanchoin, J. Löwe, R. Hegde, P. Farrell and P. Crosby for discussion and suggestions; the staff at the companies Cherry Biotech and Elvesys, in particular T. Guérinier, for their help in designing and assembling the custom microfluidics system required for this project; the members of the Electronics and Mechanical workshops of the LMB for key support; the staff at the LMB Mass Spectrometry facility for performing and analysing MS data; and A. Prasad and T. Stevens for sharing the scripts for protein disorder and kinase motif predictions, respectively. Cartoons were created using BioRender. For the purpose of open access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any author accepted manuscript version arising.Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of ‘structured’ water molecules within their hydration layers, reducing the available ‘free’ bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2, 3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function

Macromolecular condensation buffers intracellular water potential

Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2,3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.</p