ASBMB Award Articles
Outer membrane vesicles as molecular biomarkers for Gram-negative sepsis: Taking advantage of nature’s perfect packagesSepsis is an often life-threatening response to infection, occurring when host proinflammatory immune responses become abnormally elevated and dysregulated. To diagnose sepsis, the patient must have a confirmed or predicted infection, as well as other symptoms associated with the pathophysiology of sepsis. However, a recent study found that a specific causal organism could not be determined in the majority (70.1%) of sepsis cases, likely due to aggressive antibiotics or localized infections. The timing of a patient’s sepsis diagnosis is often predictive of their clinical outcome, underlining the need for a more definitive molecular diagnostic test.
Allosteric regulation by membranes and hydrophobic subsites in phospholipase A2 enzymes determine their substrate specificityLipids play critical roles in several major chronic diseases of our times, including those that involve inflammatory sequelae such as metabolic syndrome including obesity, insulin sensitivity, and cardiovascular diseases. However, defining the substrate specificity of enzymes of lipid metabolism is a challenging task. For example, phospholipase A2 (PLA2) enzymes constitute a superfamily of degradative, biosynthetic, and signaling enzymes that all act stereospecifically to hydrolyze and release the fatty acids of membrane phospholipids.
Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signalingThe simple structure of phosphatidic acid (PA) belies its complex biological functions as both a key phospholipid biosynthetic intermediate and a potent signaling molecule. In the latter role, PA controls processes including vesicle trafficking, actin dynamics, cell growth, and migration. However, experimental methods to decode the pleiotropy of PA are sorely lacking. Because PA metabolism and trafficking are rapid, approaches to accurately visualize and manipulate its levels require high spatiotemporal precision.
Practical advice for mentoring and supporting faculty colleagues in STEM fields: Views from mentor and mentee perspectivesIn 2020, the American Society of Biochemistry and Molecular Biology (ASBMB) Women in Biochemistry and Molecular Biology Committee introduced the ASBMB Leadership Awards to recognize individuals with a strong commitment to advancing the careers of women in biochemistry and molecular biology along with demonstrated excellence in research, discovery, and/or service. This innovative award recognizes efforts to mentor and support trainees and colleagues at all levels. Such a leadership award provides the opportunity to focus briefly on the important role of mentoring within the STEM disciplines.
Structural basis of substrate specificity in human cytidine deaminase family APOBEC3sThe human cytidine deaminase family of APOBEC3s (A3s) plays critical roles in both innate immunity and the development of cancers. A3s comprise seven functionally overlapping but distinct members that can be exploited as nucleotide base editors for treating genetic diseases. Although overall structurally similar, A3s have vastly varying deamination activity and substrate preferences. Recent crystal structures of ssDNA-bound A3s together with experimental studies have provided some insights into distinct substrate specificities among the family members.
The extensive and functionally uncharacterized mitochondrial phosphoproteomeMore than half a century ago, reversible protein phosphorylation was linked to mitochondrial metabolism through the regulation of pyruvate dehydrogenase. Since this discovery, the number of identified mitochondrial protein phosphorylation sites has increased by orders of magnitude, driven largely by technological advances in mass spectrometry-based phosphoproteomics. However, the majority of these modifications remain uncharacterized, rendering their function and relevance unclear. Nonetheless, recent studies have shown that disruption of resident mitochondrial protein phosphatases causes substantial metabolic dysfunction across organisms, suggesting that proper management of mitochondrial phosphorylation is vital for organellar and organismal homeostasis.
Getting there: Thyroid hormone receptor intracellular traffickingA year ago, when I first contemplated writing this article, my intent was to provide a detailed review of the contributions of the diverse community of talented scientists in my lab to the nuclear receptor research field. In the throes of a deadly pandemic, political turmoil, and Black Lives Matter, however, I found myself compelled to tell a more personal story. While I will still cover milestones in our understanding of the intracellular trafficking of the thyroid hormone receptor, now these will be set against the backdrop of my path as a woman in STEM and on being intentionally inclusive.