SRI Human
Description
SRI International’s Translational Readthrough Agents
SRI International has developed small-molecule readthrough agents to suppress premature termination codons (PTCs) in genetic diseases. These compounds target translation termination factors to restore functional protein expression.
Key Compounds
SRI-41315 demonstrated superior readthrough efficacy compared to SRI-37240, with improved pharmacokinetic properties. It synergizes with aminoglycosides (e.g., G418) to enhance CFTR activity in human bronchial epithelial cells .
Radionuclide Decorporation Agent: HOPO 14-1
HOPO 14-1, developed in collaboration with Lawrence Berkeley National Laboratory, is a hexadentate chelator designed to sequester and eliminate radioactive metals (e.g., actinides) from the body.
Key Findings
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Mechanism: Binds radionuclides via high-affinity chelation, enabling rapid urinary excretion.
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Clinical Progress:
Neuroscience and Brain Imaging: SRI24 Atlas
The SRI24 multichannel atlas is a population-averaged brain imaging template for spatial normalization and label propagation in neuroimaging studies.
Active Projects
Sleep Research and Applied Neurotechnology
SRI’s Human Sleep Program investigates sleep disorders and develops wearable technologies for monitoring sleep health. Recent work includes:
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Menopausal Insomnia: Identifying hormonal and physiological drivers of sleep disruption in menopausal women.
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Adolescent Sleep: Linking sleep patterns to brain development and mental health outcomes .
Historical Contributions
SRI International has advanced over 100 drugs into clinical trials, including:
Product Specs
MGSSHHHHHH SSGLVPRGSH MGSMAYPGHP GAGGGYYPGG YGGAPGGPAF PGQTQDPLYG YFAAVAGQDG QIDADELQRC LTQSGIAGGY KPFNLETCRL MVSMLDRDMS GTMGFNEFKE LWAVLNGWRQ HFISFDTDRS GTVDPQELQK ALTTMGFRLS PQAVNSIAKR YSTNGKITFD DYIACCVKLR ALTDSFRRRD TAQQGVVNFP YDDFIQCVMS V.
Q&A
What is the scope of SRI International's human research programs?
SRI Biosciences, a division of SRI International, conducts pioneering research across multiple domains including human sleep, immuno-oncology, drug delivery, and point-of-care diagnostics. Their human research initiatives aim to develop transformative approaches for challenging therapeutic problems through rigorous scientific methodologies . The Human Sleep Research Program, in particular, is recognized for its dual expertise in conducting both basic/clinical research studies and applied commercial R&D work in the sleep technology space .
Research at SRI follows established scientific protocols with emphasis on:
| Research Component | Implementation at SRI | Methodological Significance |
|---|---|---|
| Study Design | Interventional and observational approaches | Enables both causative and correlational analyses |
| Data Collection | Multi-modal physiological measurements | Provides comprehensive assessment of human biological processes |
| Analysis Techniques | Advanced statistical and computational methods | Allows for nuanced interpretation of complex data sets |
| Population Focus | Diverse age groups with special focus on adolescents and mid-life women | Addresses demographic-specific research questions |
What techniques are employed in SRI's human sleep studies?
SRI's Human Sleep Research Program employs a sophisticated array of techniques to gather comprehensive physiological data during sleep studies . Their methodological approach combines multiple measurement techniques with advanced analytical approaches:
| Technique | Application | Data Yield |
|---|---|---|
| Electroencephalography (EEG) | Brain activity monitoring | Neural oscillations and sleep architecture |
| Impedance Technology | Bioelectrical measurements | Tissue composition and fluid status |
| Magnetic Resonance Imaging (MRI) | Brain structure and function assessment | Anatomical and functional neural correlates |
| Beat-to-Beat Blood Pressure Monitoring | Cardiovascular function assessment | Hemodynamic regulation during sleep |
These techniques are integrated with clinical and behavioral neuropsychological data to provide a holistic understanding of sleep processes. The combination allows researchers to investigate relationships between sleep physiology and cognitive or emotional outcomes that might not be apparent through single-modality approaches .
How should researchers approach experimental design for human sleep studies?
When designing experiments for human sleep research, investigators must balance scientific rigor with practical considerations. Based on established experimental design principles, researchers should:
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Ensure adequate statistical power through appropriate trial replication. Having 3-5 trials for each variable is essential to establish data reliability and properly identify outliers .
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Allocate experimental time efficiently: 15-20 minutes should typically provide sufficient data collection opportunities while preventing participant fatigue .
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Distribute research tasks strategically among team members: not all team members need to conduct experimental procedures simultaneously; specialized roles often increase efficiency .
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Prepare contingency plans for experimental failures, focusing on thorough documentation of errors and methodological limitations .
The experimental design must account for variables specific to sleep research, including:
| Variable Type | Examples | Design Considerations |
|---|---|---|
| Physiological | Circadian rhythms, hormonal status | Time-matching, controlling for menstrual phase |
| Environmental | Temperature, noise, light | Standardized laboratory conditions |
| Psychological | Stress, anxiety, expectation effects | Pre-sleep assessment, randomization |
| Demographic | Age, sex, health status | Appropriate sample stratification |
What are common experimental errors in human sleep research and how can they be mitigated?
Recognizing and addressing potential errors is crucial for valid sleep research outcomes. Researchers should be vigilant about:
When errors do occur, researchers should document them thoroughly, explaining both the nature of the error and its potential impact on results. This documentation supports transparency and allows others to appropriately interpret findings despite methodological limitations .
How does SRI approach the study of sleep across different developmental stages?
SRI's developmental approach to sleep research recognizes the unique characteristics of sleep across the lifespan. Their research program specifically investigates:
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Developmental changes in sleep and brain structure/function across adolescence, a critical period for neuromaturation .
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Sleep characteristics and disorders in mid-life women, with attention to hormonal influences .
This developmental framework employs longitudinal and cross-sectional methodologies to capture both within-subject changes and between-group differences. The research acknowledges that sleep parameters, brain development, and cognitive/emotional processes have reciprocal relationships that evolve throughout the lifespan.
How can researchers effectively analyze contradictions in human sleep data?
Data contradictions in sleep research require systematic analytical approaches. When confronted with contradictory findings, researchers should:
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Distinguish between measurement artifacts and true physiological variability
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Employ multiple analytical methods to test the robustness of findings
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Consider individual differences that might explain apparent contradictions
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Examine potential moderating variables that could explain divergent results
SRI's approach integrates sophisticated analytical techniques with comprehensive data collection to address potential contradictions. Their methodology includes:
| Analytical Challenge | Methodological Approach |
|---|---|
| Signal Artifact vs. True Effect | Multi-modal verification across measurement techniques |
| Individual Variability | Detailed phenotyping and subgroup analyses |
| State-Dependent Effects | Analysis stratified by sleep stage or physiological state |
| Contextual Influences | Integration of environmental and psychological assessments |
What methodological considerations apply when studying insomnia in adolescents versus mid-life women?
SRI's research program specifically investigates psychophysiological mechanisms underlying insomnia pathophysiology in both adolescents and mid-life women . These distinct populations require tailored methodological approaches:
| Methodological Aspect | Adolescent Research | Mid-Life Women Research |
|---|---|---|
| Developmental Context | Rapid brain development, changing sleep architecture | Hormonal transitions, potential perimenopausal effects |
| Assessment Tools | Age-appropriate measures, parental reports | Reproductive history assessment, hormone measurements |
| Comorbidity Screening | School performance, social development | Vasomotor symptoms, mood disturbances |
| Intervention Design | School schedule consideration, parental involvement | Hormone therapy interactions, hot flash monitoring |
SRI's research highlights the importance of investigating sleep problems in women specifically, with attention to memory processing during sleep and unique physiological characteristics . This population-specific approach allows for more targeted interventions and deeper understanding of insomnia mechanisms across different demographic groups.
How should researchers navigate human subjects protocols for sleep research?
The Human Subjects System (HSS) provides a framework for reporting and updating human subjects data to NIH. Researchers should understand:
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HSS is populated by data entered on the Human Subjects and Clinical Trial Information form in applications submitted after January 25, 2018 .
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The system allows researchers to add/update study information, create/edit enrollment reports, make off-cycle corrections, convert delayed onset studies to full records, provide interim data, inform NIH of ClinicalTrials.gov registration, and export records in XML format .
For sleep research specifically, investigators must ensure:
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Appropriate documentation of sleep deprivation protocols and safety monitoring
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Clear description of overnight study procedures
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Comprehensive reporting of physiological measurement methods
What are best practices for integrating physiological and neuropsychological data in sleep research?
SRI's approach demonstrates that effective integration of multiple data streams requires:
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Synchronized data collection with precise temporal alignment of physiological and behavioral measures
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Multi-level analysis that accounts for both within-subject and between-subject variables
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Advanced statistical techniques that can handle multi-dimensional data with complex dependencies
Researchers should consider the following integration framework:
| Integration Level | Methodological Approach | Analytical Consideration |
|---|---|---|
| Data Collection | Time-synchronized multi-modal assessment | Equipment compatibility, sampling rate alignment |
| Preprocessing | Standardized cleaning protocols across modalities | Artifact handling, signal processing parameters |
| Analysis | Mixed-methods approaches combining quantitative and qualitative data | Appropriate statistical models for nested data |
| Interpretation | Theoretical frameworks that bridge physiological and psychological domains | Integration with existing literature |
What are the current research priorities in SRI's human sleep program?
Based on recent research activities, SRI's Human Sleep Research Program is currently prioritizing:
These research directions employ both interventional and observational designs to comprehensively address sleep-related questions with real-world implications.
How can researchers translate sleep research findings into practical interventions?
SRI's approach to translational sleep research demonstrates several methodological principles:
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Identifying mechanisms that can be targeted through behavioral or pharmacological interventions
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Validating findings across multiple populations to ensure generalizability
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Partnering with commercial entities to develop applied technologies based on basic science findings
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Conducting real-world validation studies to confirm laboratory findings
Their dual focus on basic/clinical research and applied R&D work enables effective translation from scientific discovery to practical application .
Product Science Overview
Sorcin is a member of the penta-EF-hand (PEF) protein family, characterized by its calcium-binding domains. It consists of two main domains:
- N-terminal domain: A flexible, glycine-rich region.
- Calcium-binding domain: Contains five EF-hand motifs, which are helix-loop-helix structures that bind calcium ions with high affinity .
The SRI gene can produce at least four alternative transcripts, resulting in different isoforms of Sorcin. The primary isoform, known as isoform A, is a 198-amino-acid-long protein .
Sorcin plays a crucial role in calcium homeostasis and excitation-contraction coupling in the heart. It modulates the activity of RYR2 calcium channels in the sarcoplasmic reticulum, contributing to the regulation of calcium levels within cardiac cells . Upon binding calcium, Sorcin undergoes a conformational change that allows it to interact with its molecular targets .
Sorcin has been implicated in multidrug resistance in cancer cells. It has been identified as a binding partner of TRAP1, a mitochondrial chaperone, in human colorectal carcinoma cells. This interaction suggests that Sorcin may play a role in the TRAP1-associated signaling pathway, contributing to the cytoprotective functions in cancer cells .
