Proteomics Overview and Applications

Proteomics Overview

• Proteomics is the large-scale study of proteins, including their composition, structures, functions, and interactions within cells.
• This study is more complex than genomics because protein expression changes over time and with environmental conditions, while a genome is largely constant.
• Genomics provides an estimate of protein expression, but proteins often work together, and proteomics aims to identify interacting proteins.

Applied Proteomics

• Proteomics involves studying genes, messenger RNA (mRNA), and proteins.
• The process begins with genomic information (14,000 genes), followed by transcriptomic analysis (mRNA).
• This leads to proteomic analysis, which examines the hundreds of protein forms per cell type.

Proteomics Applications

• Used in pharmaceutical industry for drug development and design.
• Used in biomedicine, oncology, and agriculture/food microbiology.

Protein Design (Pharmaceutical Sector)

• Protein design is the creation of new proteins with specific properties, achieved through manipulating amino acid sequences.

• This process combines computational modeling, laboratory experiments, and interdisciplinary knowledge.

• Protein design can involve creating molecules with desired 3D structures and functions, which is a reverse process of protein structure prediction.

• Understanding protein folding principles is crucial in creating effective protein design solutions.

• In medicine, design is used for therapeutics with high specificity and low toxicity.

• Examples include proteins selectively binding to cancer cells, as well as those inhibiting viral infection.

• Antibody production traditionally involves injecting a target protein into a lab animal, letting the immune system produce antibodies, and purifying the result.

• A downside to this approach is that antibodies from another species might be rejected by a human body.

• Adjustments to the antibody sequence to resemble human sequences can solve this issue, but may compromise its structure.

• In silico design utilizes bioinformatics and computational modeling to bypass these steps, saving considerable time in protein design processes.

Drug Design and Proteomics

• Proteomics is the systematic study and characterization of proteins in biological systems. Most drugs act at the protein level, making proteomics a central part of drug development.
• Drug design using proteomics involves drug discovery by examining proteins connected to a disease to find suitable targets, lead validation, drug mode of action investigation, and chemical development.

Protein synthesis inhibitors

• Protein synthesis inhibitors halt or slow cell growth by interfering with protein generation processes.
• An example is tyrosine kinase inhibitors (TKIs), which are a form of targeted therapy acting by interfering with signal transduction leading to cell growth and division.

Protein Identification and Biomarkers

• Clinical proteomic studies aim to discover biomarkers for identifying diseases with high accuracy, reproducibility, and a high sample rate.
• Extensive proteome coverage of complex samples is necessary to detect proteins with varying concentrations.
• High-throughput MS (mass spectrometry)-based profiling techniques like MALDITOF and SELDI allow rapid detection of molecular masses and help screen small amounts of clinical samples for biomarkers.
• Biomarkers are proteins that can indicate normal or pathogenic biological processes or pharmacologic responses to treatments. These are crucial for fundamental research and clinical applications.
• Qualitative biomarkers are used for yes/no diagnoses, whereas quantitative biomarkers use a threshold for analysis.
• Proteomics is helpful for identifying protein biomarkers that can be used to detect or diagnose diseases, even before symptoms appear, which could ultimately help treatment development.
• Proteomic studies aim to achieve a 'bio-signature' from protein expression patterns across different biological fluids, which can be effectively used for pathology diagnosis.

Proteomics in Agriculture/Food

• Proteomics is applied in food technology to characterize and standardize raw materials.
• Crucial for detecting potential microbial contamination and ensuring food safety.
• Proteomics is employed in studying and characterizing proteins in food groups like milk, meat, and cereals to identify and potentially utilize any unique protein biomarkers that could indicate quality issues or other properties.
• In agricultural applications, proteomics is used to study plants and plant traits, and underlying mechanisms like resistance to stresses, improving seed quality. This method enables a better understanding of how proteins interact to manage and protect crops against biotic or abiotic stressors.

Evolution

• Recent technological advances in separation techniques combined with mass spectrometers have made proteomic analysis crucial for understanding cellular mechanisms and protein identification.
• Increased sensitivity and resolution in proteomics make it an essential tool in biological research.