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Science Lab

Publications

Artificial intelligence for natural product drug discovery

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artifcial intelligence approaches such as machine learning have led to exciting developments in the computational drug design feld, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to efectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation.

Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming

Over the past decade, there has been a dramatic increase in eforts to ameliorate aging and the diseases it causes, with transient expression of nuclear reprogramming factors recently emerging as an intriguing approach. Expression of these factors, either systemically or in a tissuespecifc manner, has been shown to combat age-related deterioration in mouse and human model systems at the cellular, tissue and organismal level. Here we discuss the current state of epigenetic rejuvenation strategies via partial reprogramming in both mouse and human models. For each classical reprogramming factor, we provide a brief description of its contribution to reprogramming and discuss additional factors or chemical strategies. We discuss what is known regarding chromatin remodeling and the molecular dynamics underlying rejuvenation, and, fnally, we consider strategies to improve the practical uses of epigenetic reprogramming to treat aging and age-related diseases, focusing on the open questions and remaining challenges in this emerging feld.

Alphafold's Breakthrough

Proteins are the building blocks of life. They are vital to our existence with roles in almost all the biochemical processes. A protein is made up of one or more linear chains of amino acids (a singular chain is called a poly-peptide), Figure 1B. All amino acids share a basic structure, which consists of a central carbon atom, also known as the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom, this is known as the residual (R) group, this group determines the identity of the amino acid and its chemical properties, Figure 1A. There are 20 types of amino acids commonly found in proteins. A protein is a complex substance that consists of amino-acid residues joined by peptide bonds (Merriam-Webster, 2020), a large bio-molecule consisting of one or more long chains of amino acid residues.

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