A pinboard by
Jan Peyper

PhD candidate, University of Cape Town


Global proteomics models functional systems biology of healthy/clinically-derived neutrophils.

Our immune system - comprising many different and interacting cell types - is what protects us from disease. It communicates bidirectionally (and powerfully) with all other body systems to determine overall health. The proteins present in an immune cell determine its function.

We identify and quantify all proteins present in an important and under-studied human immune cell type (neutrophils) from both healthy volunteers and TB/HIV-coinfected patients.

This facilitates modelling of the functional state and dynamics of these cells, which helps us to understand how TB/HIV coinfection and co-treatment impact normal neutrophil function. We hope to extend this research to understand neutrophil function as part of the complex immune cell network operating in the body.

We are particularly interested in understanding the role of neutrophils and other immune cells in complex human diseases whose underlying pathogenic mechanisms are not well understood, but are probably rooted in immune dysfunction.

Currently, we are trying to understand a systemic inflammatory syndrome called tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS), which causes significant morbidity and mortality.

TB-IRIS affects up to 50% of patients undergoing co-treatment for both TB and HIV, and neither a reliable diagnostic test nor a specific treatment exist.

Since ~80% of the world's TB/HIV coinfected population resides in sub-Saharan Africa, TB-IRIS is a particularly common problem in local areas with good access to antiretroviral therapy, such as the Western Cape.

We anticipate that an improved understanding of the immune causes of TB-IRIS will facilitate better risk-stratification, prevention, diagnosis, prognostication, and treatment.

However, the impact of research into human immune function has a much broader scope than just TB-IRIS. A deeper understanding of normal dynamic immune functioning and how this becomes dysregulated will enable public health strategies which focus more on prevention than cure, and on extremely early detection and treatment of disease.

Furthermore, given their under-studied status, neutrophils are also excellent candidates in which to observe the remaining human proteins (predicted from the genome) for whose existence experimental evidence has never before been found.

In general, systems biology strategies (such as proteomics) are our best tools for mapping and optimising the complex and dynamic function of the human body.


The quest of the human proteome and the missing proteins: digging deeper.

Abstract: Given the diverse range of transcriptional and post-transcriptional mechanisms of gene regulation, the estimates of the human proteome is likely subject to scientific surprises as the field of proteomics has gained momentum worldwide. In this regard, the establishment of the "Human Proteome Draft" using high-resolution mass spectrometry (MS), tissue microarrays, and immunohistochemistry by three independent research groups (laboratories of Pandey, Kuster, and Uhlen) accelerated the pace of proteomics research. The Chromosome Centric Human Proteome Project (C-HPP) has taken initiative towards the completion of the Human Proteome Project (HPP) so as to understand the proteomics correlates of common complex human diseases and biological diversity, not to mention person-to-person and population differences in response to drugs, nutrition, vaccines, and other health interventions and host-environment interactions. Although high-resolution MS-based and antibody microarray approaches have shown enormous promises, we are still unable to map the whole human proteome due to the presence of numerous "missing proteins." In December 2014, at the Indian Institute of Technology Bombay, Mumbai the 6(th) Annual Meeting of the Proteomics Society, India (PSI) and the International Proteomics Conference was held. As part of this interdisciplinary summit, a panel discussion session on "The Quest of the Human Proteome and Missing Proteins" was organized. Eminent scientists in the field of proteomics and systems biology, including Akhilesh Pandey, Gilbert S. Omenn, Mark S. Baker, and Robert L. Mortiz, shed light on different aspects of the human proteome drafts and missing proteins. Importantly, the possible reasons for the "missing proteins" in shotgun MS workflow were identified and debated by experts as low tissue expression, lack of enzymatic digestion site, or protein lost during extraction, among other contributing factors. To capture the missing proteins, the experts' collective view was to study the wider tissue range with multiple digesting enzymes and follow targeted proteomics workflow in particular. On the innovation trajectory from the proteomics laboratory to novel proteomics diagnostics and therapeutics in society, we will also need new conceptual frames for translation science and innovation strategy in proteomics. These will embody both technical as well as rigorous social science and humanities considerations to understand the correlates of the proteome from cell to society.

Pub.: 02 May '15, Pinned: 31 Jul '17