حصة محمد سليمان العبيد

الاسم الاول: 
حصة
اسم العائلة: 
العبيد
الدرجة العلمية: 
دكتوراة
مجال الدراسة: 
العلوم والتقنية
المؤسسة التعليمية: 
University of Bristol

 

 

مجال التميز

تميز دراسي وبحثي + جائزة تفوقية

 

 

البحوث المنشورة

 

البحث (1):

 

عنوان البحث:

Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics

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تاريخ النشر:

  27 February 2017

موجز عن البحث:

Information theoretic approaches can be used to quantify information transfer via cell signaling networks. In this study, we do so for gonadotropin-releasing hormone (GnRH) activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) in large numbers of individual fixed LβT2 and HeLa cells. Information transfer, measured by mutual information between GnRH and ERK or NFAT, was <1 bit (despite 3-bit system inputs). It was increased by sensing both ERK and NFAT, but the increase was <50%. In live cells, information transfer via GnRH receptors to NFAT was also <1 bit and was increased by consideration of response trajectory, but the increase was <10%. GnRH secretion is pulsatile, so we explored information gained by sensing a second pulse, developing a model of GnRH signaling to NFAT with variability introduced by allowing effectors to fluctuate. Simulations revealed that when cell–cell variability reflects rapidly fluctuating effector levels, additional information is gained by sensing two GnRH pulses, but where it is due to slowly fluctuating effectors, responses in one pulse are predictive of those in another, so little information is gained from sensing both. Wet laboratory experiments revealed that the latter scenario holds true for GnRH signaling; within the timescale of our experiments (1 to 2 hours), cell–cell variability in the NFAT pathway remains relatively constant, so trajectories are reproducible from pulse to pulse. Accordingly, joint sensing, sensing of response trajectories, and sensing of repeated pulses can all increase information transfer via GnRH receptors, but in each case the increase is small. 

 

 

البحث (2): 

 

عنوان البحث:

Gonadotropin-releasing hormone signaling: An information theoretic approach 

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تاريخ النشر:

  29 July 2017

موجز عن البحث:

Gonadotropin-releasing hormone (GnRH) is a peptide hormone that mediates central control of reproduction, acting via G-protein coupled receptors that are primarily Gq coupled and mediate GnRH effects on the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. A great deal is known about the GnRH receptor signaling network but GnRH is secreted in short pulses and much less is known about how gonadotropes decode this pulsatile signal. Similarly, single cell measures reveal considerable cell-cell heterogeneity in responses to GnRH but the impact of this variability on signaling is largely unknown. Ordinary differential equation-based mathematical models have been used to explore the decoding of pulse dynamics and information theory-derived statistical measures are increasingly used to address the influence of cell-cell variability on the amount of information transferred by signaling pathways. Here, we describe both approaches for GnRH signaling, with emphasis on novel insights gained from the information theoretic approach and on the fundamental question of why GnRH is secreted in pulses. 

 

 

البحث (3):

 

عنوان البحث:

Exploring Dynamics and Noise in Gonadotropin-Releasing Hormone (GnRH) Signaling

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تاريخ النشر:

13 November 2018

موجز عن البحث:

Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes. These are Gq-coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. FSH and LH control steroidogenesis and gametogenesis in the gonads so GnRH mediates control of reproduction by the central nervous system. GnRH is secreted in short pulses and the effects of GnRH on its target cells are dependent on the dynamics of these pulses. Here we provide a brief overview of the signaling network activated by GnRH with emphasis on the use of high content imaging for their examination. We also describe computational approaches that we have used to simulate GnRH signaling in order to explore dynamics, noise, and information transfer in this system.

 

 

البحث (4):

 

عنوان البحث:

Role of the posterodorsal medial amygdala in predator odour stressinduced puberty delay in female rats

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تاريخ النشر:

09 April 2019

موجز عن البحث:

Puberty onset is influenced by various factors, including psychosocial stress. The present study investigated catodour stress on puberty onset and oestrous cyclicity in rats. Female weanling rats were exposed to either soiled cat litter or fresh unused litter for 10 consecutive days. Following vaginal opening (VO), rats were smeared for 14 days to determine oestrous cyclicity. Anxietylike behaviour was assessed using standard anxiety tests. Brains were collected to determine corticotrophinreleasing factor (CRF), CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) mRNA in the paraventricular nucleus (PVN), as well as the central nucleus of the amygdala (CEA) and the medial nucleus of the amygdala (MEA). Cat odour delayed VO and first oestrus, disrupted oestrous cycles and caused anxiogenic responses. Cat odour elicited increased CRF mRNA expression in the PVN but not in the CeA. CRFR1 and CRFR2 mRNA levels in the PVN and CeA were unaffected by cat odour; however, CRFR1 mRNA levels were decreased in the MeA. The role of CRF signalling in the MeA, particularly its posterodorsal subnucleus (MePD), with respect to pubertal timing was directly examined by unilateral intraMePD administration of CRF (0.2 nmol day1 for 14 days) via an osmotic minipump from postnatal day 24 and was shown to delay VO and first oestrus. These data suggest that CRF signalling in the MePD may be associated with predator odourinduced puberty delay.

 

 

المؤتمرات العلمية:

 

المؤتمر (1):

 

عنوان المؤتمر:

The annual meeting of the British Society for Neuroendocrinology

تاريخ الإنعقاد:

10 - 12 September 2017

مكان الإنعقاد:

Nottingham, UK

طبيعة المشاركة:

Oral presentation

عنوان المشاركة:

Measuring information transfer via gonadotrophin-releasing hormone receptors

ملخص المشاركة:

Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotrophs, causing a (largely) PKC-mediated activation of ERK, and a Ca2+-mediated activation of Nuclear Factor of Activated T-cells (NFAT), both of which mediate GnRH effects on gonadotropin expression. We monitor their activation by high content imaging (fluorescence staining for ppERK and nuclear translocation of an NFAT1c-EFP reporter) in LbT2 gonadotroph cells. We also express Egr1-zsGREEN and/or NFAT-RE-asRED reporters as transcriptional readouts for ERK and NFAT activation, respectively. Single cell measures reveal high cell-to-cell variability, and information theoretical approaches can be used to explore its influence on information transfer. Here we use Mutual Information (MI) between GnRH and our single cell experimental readouts (I(response; GnRH)) as measures of information transfer via GnRH receptors. An MI of 1Bit means that the system can unambiguously distinguish two (identically distributed) inputs and we routinely provide a 3Bit input (i.e., 8=23 GnRH concentrations). However, the MI between GnRH and these readouts was always <1Bit. Joint sensing of ERK and NFAT increased MI but the effect was small and joint MI values were also <1. Information transfer could be increased by sensing response trajectory and when we tracked NFAT1c-EFP in individual cells I(NFAT-nuclear fraction; GnRH) values were maximal (~0.45Bit) at ~30min and slightly higher values (~0.65Bit) were obtained by consideration of trajectories. Thus, LbT2 cells appear to be unreliable sensors of GnRH concentration because most available information is lost through signalling and, although information transfer was increased by joint sensing and trajectory sensing, the increases seen were small.

 

 

المؤتمر (2):

 

عنوان المؤتمر:

Europhysiology 2018

تاريخ الإنعقاد:

14 - 16 September 2018

مكان الإنعقاد:

London, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Quantification of information transfer via gonadotrophin-releasing hormone receptors (GnRHR) reveals a marked loss of information through signalling

ملخص المشاركة:

Gonadotropin-releasing hormone (GnRH) is a hypothalamic neuropeptide that acts via GnRHR on the pituitary gonadotrope. It is secreted in pulses and acts via GnRHR to activate ERK and Nuclear Factor of Activated T-cells (NFAT). Both of which mediate GnRH effects on the synthesis of reproductive hormones. Using automated fluorescence microscopy, effects of GnRH on cell signalling in individual cells can be quantified revealing marked cell-cell heterogeneity. Information theoretic approaches, which consider cell-cell heterogeneity and its impact on information transfer, can be used to quantify information transfer via cell signalling pathways. Here we use the mutual information (MI) between GnRH concentration and measured responses (I(response; GnRH)) as a measure of information transfer via GnRHR. MI is measured in Bits, with an MI of 1 Bit indicating a system that can unambiguously distinguish between two inputs. Initially, we did this in fixed LbT2 cells (gonadotrope-derived cells). The cells were stimulated with various concentrations of GnRH (0-10-6M) before staining for ppERK (immunohistochemistry), and in some experiments, cells were infected with recombinant adenovirus for expression of NFAT- EFP. As Ca2+ causes NFAT to translocate to the nucleus, the nuclear fraction (NF) provides a readout for elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i) by GnRH. Our data, therefore, suggest that most information from the environment is lost through signalling. The I(ppERK; GnRH) and I(NFAT-NF; GnRH) values were always <1Bit despite 3Bit input. Joint sensing of ppERK and NFAT-NF increased slightly MI values [1,2], suggesting that, by ignoring response dynamics, information transfer is underestimated. Therefore, using live cell measurements and MI calculations taking response trajectory into account, NFAT-EFP translocation was tracked in response to a single pulse of GnRH. The I(NFAT-NF; GnRH) values were ~0.5 Bit at 30 min and remained elevated for 60 min. Taking response trajectories into account increased MI values to ~0.65 Bit. We also tracked NFAT-EFP translocation responses in cells receiving two pulses of GnRH and found that the information gain from the second pulse was small. Similar experiments were performed using Fluo-4 measurements of [Ca2+]i. The I(Ca2+; GnRH) values were ~0.8 Bit, 24sec after stimulation, reducing to ~0.66 Bit after 2 min. These values were increased to 1Bit by consideration of trajectories. Thus, LbT2 cells are unreliable sensors of GnRH concentration because a considerable amount of information is lost through signalling. Although joint sensing, trajectory sensing and sensing repeated pulses increased information transfer, this was typically <20% suggesting that most information is lost early in the GnRH signalling cascade, prior to Ca2+ mobilization.

 

 

المؤتمر (3):

 

عنوان المؤتمر:

Society for Endocrinology BES 2018

تاريخ الإنعقاد:

19 - 21 November 2018

مكان الإنعقاد:

Scotland, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Measuring information transfer via gonadotrophin-releasing hormone receptors (GnRHR) shows a remarkable loss of information through signalling

ملخص المشاركة:

Gonadotropin-releasing hormone (GnRH) is a hypothalamic neuropeptide that acts via GnRHR on the pituitary gonadotrope. It is secreted in pulses and acts via GnRHR to activate ERK and Nuclear Factor of Activated T-cells (NFAT), mediating GnRH effects on gonadotropin expression. We monitor their activation by high content imaging (fluorescence staining for ppERK and nuclear translocation of an NFAT1c-EFP reporter) in fixed LbT2 gonadotroph cells. Single cell measures reveal high cell-cell heterogeneity, and information theoretical approaches can be used to explore its influence on information transfer. Here we use Mutual information (MI) between GnRH concentration and measured responses (I(response; GnRH)) to measure (in Bits) information transfer via GnRHR. One bit of information can resolve two different signal values. However, the MI values were always <1Bit despite 3Bit input. Joint sensing of ERK and NFAT increased MI values, but the increase was modest, suggesting that, by ignoring response dynamics, information transfer is underestimated. Therefore, using live cell measurements and MI calculations taking response trajectory into account, NFAT-EFP translocation was tracked in response to a single pulse of GnRH. The I(NFAT-NF; GnRH) was 0.4Bit at 30min and increased to 0.54 Bit by consideration of trajectories. We also tracked NFAT-EFP translocation responses in cells receiving two pulses of GnRH and found that the information gained from the second pulse was little. Similar experiments were performed using Fluo-4 measurements of [Ca2+]i. The I(Ca2+; GnRH) was 0.8Bit, 24sec after stimulation, and increased to 1Bit by sensing trajectories. Thus, LbT2 cells are unreliable sensors of GnRH concentration because a considerable amount of information is lost through signalling. Although joint sensing, trajectory sensing and sensing repeated pulses increased information transfer, this was typically <20% suggesting that most information is lost early in the GnRH signalling cascade, prior to Ca2+ mobilisation.

 

 

جوائز التكريم:

 

الجائزة (1):

 

مسمى الجائزة:

Best Poster Prize Presentation

الجهة المانحة:

University of Bristol

تاريخ الجائزة:

11 April 2018

مجال التكريم:

Best poster presentation at the Showcase and Network Day hosted by the Bristol Neuroscience Research Network at the University of Bristol.

 

 

AttachmentSize
1-The annual meeting of the British Society for Neuroendocrinology.pdf101.22 KB
2-2-Europhysiology meeting-attendance.pdf227.57 KB
3-SfE BES 2018 - Certificate of Attendance.pdf175.59 KB
Neurosciencw-poster prize presentation.pdf364.94 KB