Showing 11 ideas for tag "biology"

Goal 2: Reduce Human Disease

UNDERSTANDING SLEEP AND CIRCADIAN DISORDERS AT A BASIC MECHANISTIC LEVEL

We need to understand sleep and circadian disorders at a more mechanistic level. This applies to both the pathogenesis of these disorders and to their impact on health. New neurobiological and molecular tools facilitate this research. The focus needs to be not only in brain but also the impact of these disorders on future of peripheral organs. The elucidation of the fundamental functions of sleep and the impact of... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Much of the research on the consequences of sleep/circadian disorders has focused on their consequences or behavior. This type of research needs to be continued and there are new opportunities in this area. These behavioral studies need to be established in model systems to parallel studies in humans. In addition, new neurobiological approaches, including optogenetics and use of DREAD, provide new tools for this investigation. Moreover, we now have powerful molecular tools to evaluate effects of sleep/circadian disorders both in humans and animal models. These include microarrays, RNA seq, etc. Moreover, genetic studies, e.g., in restless legs syndrome, have identified gene variants conferring risk for the disorder. We do not know, however, how these particular genes are involved in the pathogenesis of the disorder or whether they represent potentially targets for drug intervention. There is a need for studies both in animal models and in humans to elucidate the function of these genes. Studies in other areas are obtaining stem cells from biopsies in patients and then turning these into relevant target cells such as neurons to elucidate gene function using in vitro approaches.
The impact of this effort will be the following:

a. Taking our understanding of pathogenesis of sleep and circadian disorders to a new level.
b. Understanding the consequences of sleep and circadian disorders on different end organs at a more in-depth molecular level.

Feasibility and challenges of addressing this CQ or CC

The sleep and circadian field have access to all the major cells systems for these studies—C. elegans, aplysia, Drosophila, zebra-fish, mice, etc. Moreover, there are already gene variants identified in human studies which require follow-up functional studies. The field has the expertise in all of the techniques described above. Moreover, there are more validated animal models for many of the common sleep disorders. Thus, this new approach is very feasible. 

Name of idea submitter and other team members who worked on this idea Sleep Research Society

Voting

179 net votes
232 up votes
53 down votes
Active

Goal 2: Reduce Human Disease

The effects of environmental factors on heart, lung, blood, sleep disease development across the lifespan

How do growth, development, exposure, and behavior affect heart, lung, blood, sleep disease development and outcome throughout the lifespan?

 

How do you improve organ function/capacity during childhood?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Defining earliest elements of disease and strategies for prevention

Feasibility and challenges of addressing this CQ or CC

If we don’t start now, it will never get done
. Challenges:
• Determine if elements of cell aging, including stem cell aging and senescence, affect disease progression and the effectiveness of therapeutic interventions
• Can we develop iPS based or other cell based bioengineered tools to more precisely define cellular and molecular responses to particular exposures?
• How do we identify, prioritize and measure relevant environmental exposures?

Name of idea submitter and other team members who worked on this idea NHLBI Staff

Voting

12 net votes
32 up votes
20 down votes
Active

Goal 2: Reduce Human Disease

How to maximize the opportunities and promise of emerging omics research? Develop scientific commons

In the late 20th century, the NHLBI cohorts were created as separate entities with specific research goals. The NHLBI’s funding of GWAS served as a powerful incentive for collaboration among the NHLBI-funded cohort studies. The creation of a scientific commons would provide a major national resource comprising the participants, their deeply phenotyped data, their biological samples, and the investigator expertise to... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Advance discovery and treatment

Feasibility and challenges of addressing this CQ or CC

Feasible with few challenges. The system would need infrastructure support.

Name of idea submitter and other team members who worked on this idea Psaty & Tracy

Voting

6 net votes
20 up votes
14 down votes
Active

Goal 2: Reduce Human Disease

Vascular biology and the pathophysiology of sepsis

Unravel the cellular & molecular mechanisms related to the vascular biology of sepsis and related cardiovascular collapse. The goal is to develop a new scientific framework for the prevention of sepsis related morbidity and mortality by applying novel approaches to discover new targets for biomarkers and therapy by promoting multidisciplinary research required for scientific cross-talk between complementary research disciplines... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

Voting

4 net votes
8 up votes
4 down votes
Active

Goal 2: Reduce Human Disease

National network to study the pathobiology of sepsis

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

Voting

2 net votes
4 up votes
2 down votes
Active

Goal 2: Reduce Human Disease

Defining the developmental abnormalities leading to birth defects

Can we define the developmental abnormalities leading to birth defects and extrapolate that knowledge to define strategies for regeneration?

 

How can we recognize initiation of disease earlier?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea NHLBI Staff

Voting

-1 net votes
8 up votes
9 down votes
Active

Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

As detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

Voting

-2 net votes
9 up votes
11 down votes
Active

Goal 2: Reduce Human Disease

Novel methods to diagnose and treat microvascular ischemia

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Development of effective diagnostics would lead to improved treatments for myocardial and non-myocardial microvascular ischemia, and also advance understanding to extend the advance beyond this setting.

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

Voting

0 net votes
2 up votes
2 down votes
Active

Goal 2: Reduce Human Disease

Redox regulation of cardiovascular and lung disease through thiols

Redox imbalance as represented by alterations in oxidative versus reductive stresses are well appreciated to occur during nearly all forms of cardiovascular and lung diseases. However, specific molecular mechanisms responsible for these changes remain largely unknown and poorly organized. Study of redox biology principals has revealed that protein cysteine thiols are a unique target for redox posttranslational modifications... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Protein cysteine thiols are recognized to be important for multiple signaling and cell biology functions due to unique properties of oxidation/reduction resulting in a 'thiol switch'. However, oxidative modifications of thiols are highly complex involving nitrosation, sulfhydration, sulfenylation, and glutathiolyation among many others. It has become increasingly clear that these posttranslational modifications are associated with cardiovascular and pulmonary pathophysiology. Yet, many important questions remain such as: how these thiol modifications occur during disease and differ from health? How do these thiol switches impact protein function involved in cellular pathophysiology? And can thiol switch manipulation be exploited for therapeutic purposes to maintain cellular and organ health or treat disease? In order to begin to answer these questions, careful and comprehensive investigations are required to understand thiol-switching principals employing a host of molecular, biochemical and pathophysiological approaches.

Feasibility and challenges of addressing this CQ or CC

Given the significant advances in quantitative analytical chemical and molecular techniques, molecular redox mediators and pathways, non-invasive imagine modalities and comprehensive translational study designs; multiple fields are uniquely poised that could provide significant insight into this critical challenge. Primary objectives would be to establish consensus analytical methodologies, chemical and molecular biology approaches, and cellular and animal models in conjunction with rigorous clinical investigations. Results from efforts at understanding the importance of ‘thiol switches’ will make significant clinical impact on cardiovascular and lung pathogenesis and would feasibly be accomplished in 5-10 years.

Voting

-5 net votes
5 up votes
10 down votes
Active