Genetic Engineering seminars

David Baker presents recent advances in designing proteins for functions that natural evolution has not been required to solve. The approach begins with a desired structure or activity and uses deep learning to propose amino acid sequences expected to realise it. The resulting designs are translated into synthetic genes, produced as proteins and tested experimentally. The lecture connects computational design with laboratory characterisation, explaining how the combination can create new molecular functions relevant to medicine, technology and sustainability. Its focus is the construction and evaluation of proteins from scratch, extending the protein-design research recognised by the 2024 chemistry prize.

Shimon Sakaguchi, Mary E. Brunkow and Fred Ramsdell explain how peripheral immune tolerance prevents the immune system from attacking the body. Sakaguchi follows the identification of regulatory T cells, the CD25 marker, and the relationship between central tolerance and active suppression of self-reactive cells. He considers how changing regulatory T-cell activity could support cancer treatment and transplantation. Brunkow describes genetic investigation of scurfy mice, identification of FOXP3, and the connection between mutations in this gene and human IPEX syndrome. The work establishes a molecular basis for the development and function of regulatory T cells. Ramsdell traces the move from these basic discoveries toward therapeutic strategies, including engineering a patient’s regulatory T cells to target inflammation in rheumatoid arthritis. He discusses early clinical investigation and the ambition of restoring immune balance; these approaches are presented as developing treatments rather than established cures.

Virginijus Šikšnys traces genome-editing tools to bacterial antiviral defence. Programmable CRISPR-Cas nucleases offer powerful ways to alter DNA, but delivery, unintended effects, immune interactions and insertion efficiency remain challenges. The lecture discusses compact TnpB nucleases and how further study of defence systems may reveal useful enzymatic functions.

How do cortical circuits acquire new dynamics that drive learned movements? This webinar will focus on mouse premotor cortex in relation to learned lick-timing and explore high-density electrophysiology using our silicon neural probes alongside region and cell-type-specific acute genetic manipulations of proteins required for synaptic plasticity.

Matthew Cobb uses the history of heredity to question the idea that scientific revolutions are instantly recognisable. The lecture follows changing ideas about inheritance, Mendel’s experiments and their rediscovery, evidence for DNA’s genetic role, the double helix and genetic engineering. Even major discoveries did not immediately settle contemporary debates: protein-based accounts of inheritance persisted after 1953, and evidence for DNA’s role in multicellular organisms developed later. These examples show how retrospective accounts can compress gradual changes into apparently decisive moments.

Detecting the direction of image motion is important for visual navigation, predator avoidance and prey capture, and thus essential for the survival of all animals that have eyes. However, the direction of motion is not explicitly represented at the level of the photoreceptors: it rather needs to be computed by subsequent neural circuits, involving a comparison of the signals from neighboring photoreceptors over time. The exact nature of this process represents a classic example of neural computation and has been a longstanding question in the field. Much progress has been made in recent years in the fruit fly Drosophila melanogaster by genetically targeting individual neuron types to block, activate or record from them. Our results obtained this way demonstrate that the local direction of motion is computed in two parallel ON and OFF pathways. Within each pathway, a retinotopic array of four direction-selective T4 (ON) and T5 (OFF) cells represents the four Cartesian components of local motion vectors (leftward, rightward, upward, downward). Since none of the presynaptic neurons is directionally selective, direction selectivity first emerges within T4 and T5 cells. Our present research focuses on the cellular and biophysical mechanisms by which the direction of image motion is computed in these neurons.