Tue 01 Apr 14:30: The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines
A scientific challenge is to understand biological pathways and to exploit the targets within them for therapeutic development. Coding and non-coding RNAs both directly cause disease, whether by mutation or aberrant expression. Akin to proteins, RNA structure often dictates its function in health or dysfunction in disease. RNA , however, is generally not considered a target for small molecule chemical probes and lead medicines, despite its immense potential. The focus of our research program is to uncover fundamental principles that govern the molecular recognition of RNA structures by small molecules to enable design of chemical probes that targeting disease relevant RNA structures to perturb and study their function.
I will describe using evolutionary principles to identify molecular recognition patterns between small molecules and RNA structures by studying the binding of RNA fold libraries to small molecule libraries. These interactions are computationally mined across the human transcriptome to define cellular RNAs with targetable structure. Such an approach has afforded bioactive interactions that have uncovered new biology, where the small molecules bind to functional structures within a target RNA . We have devised a strategy to imbue biologically silent RNA -small molecule interactions with cellular activity. Chimeras comprising an inactive small molecule and ribonuclease recruiter trigger targeted degradation of disease-causing RNAs. These degraders affect the biology of RNA in specific ways in cells and in mouse models of various diseases and can rationally reprogram protein-targeted medicines for RNA . Lastly, we have recently devised unbiased transcriptome wide approaches to define the RNA bound by small molecules is live cells. This allows us to study the RNA targets that are bound by small molecules, the selectivity of these interactions, and ways in which compounds of various types can modulate disease biology.
- Speaker: Matthew Disney - Scripps Research Institute
- Tuesday 01 April 2025, 14:30-15:30
- Venue: Department of Chemistry, Cambridge, Pfizer lecture theatre.
- Series: Biological Chemistry Research Interest Group; organiser: Xani Thorman.
Tue 06 May 14:30: Big Picture Talk: Bhopal 40 years on - What have we learned?
Our departmental seminar series, Bigger Picture Talks, runs throughout the academic year, inviting thought-leaders from across the world driving significant advances in our impact areas of energy, health and sustainability to share and discuss their work with us.
This talk will hear from alumni Professor Fiona Macleod, Professor of Process Safety at the University of Sheffield, who will talk about safety in the chemical engineering industry, using the worst disaster in history as a lens for why safety matters.
On the night of 2 and 3 December 1984 a toxic gas release from the Union Carbide pesticide factory in Bhopal, India caused thousands of deaths and hundreds of thousands of life-changing injuries. Forty years later, the rusting factory equipment still towers above buried hazardous waste in the abandoned factory. I visited the site of the former Union Carbide site in Bhopal India to try to understand what went so horribly wrong.
1. What caused the worst accident in the history of the chemical industry? 2. Why was the accident never properly investigated? 3. What can we learn about process safety from revisiting the accident? 4. Why has no clean-up been undertaken in 40 years?
- Speaker: Professor Fiona Macleod
- Tuesday 06 May 2025, 14:30-15:15
- Venue: Lecture Theatre 1, Department of Chemical Engineering and Biotechnology, West Cambridge Site.
- Series: Chemical Engineering and Biotechnology; organiser: ejm94.
Wed 23 Apr 14:00: Ocean dynamics in the Ross Ice Shelf cavity from in situ observations
The future response of ice shelves to climate through ocean warming is a key unknown for climate projections, especially global sea level rise. The Ross Ice Shelf ocean cavity is one of the least observed regions in the ocean, with its broad circulation patterns primarily inferred from remotely sensed estimates of tides, bathymetry, and melt rates. I aim to advance our understanding of the ocean cavity under the Ross Ice Shelf – the southern-most and largest-by area of all Earth’s ice shelves. To achieve this, I analyzed a multi-year hydrographic moored timeseries from the central Ross Ice Shelf cavity (80◦39.497′S, 174◦27.678′E). These data help address three key processes: (i) the general circulation; (ii) the appearance and impact of baroclinic eddy events; and (iii) tidal modulation of the ice-ocean boundary layer structure and the implications for ice melting. In terms of circulation and the inter-annual changes, stronger melting/refreezing occurred between late September 2019 to late December 2019, which is linked to the inter-annual sea ice production in the Ross Ice Shelf Polynya. Notably, cold-water interleaving in the mid-water column exhibits distinct seasonality. An analysis of baroclinic eddies identifies coherent structures that are around 22 km in diameter with a velocity scale of between 0.8 and 1.8 cm/s. The thermohaline structure of the eddies suggests that they have the potential to entrain High Salinity Shelf Water from the benthic water column to the mid-water column. On the question of tidal modulation of the ice shelf-ocean interaction, the results suggest that tides modulate the melt rate by altering the boundary layer structure over a spring-neap cycle. These new findings demonstrate the rich variability within the Ross Ice Shelf ocean cavity, ranging from large interannual-seasonal scales, through to multi-week eddy scales and then down to tidal and mixing timescales.
- Speaker: Yingpu Xiahou, University of Auckland
- Wednesday 23 April 2025, 14:00-15:00
- Venue: BAS Seminar Room 330b.
- Series: British Antarctic Survey - Polar Oceans seminar series; organiser: Dr Birgit Rogalla.
Fri 28 Mar 14:00: Interventions and Counterfactuals for the Working Programmer
Correlation famously does not imply causation! But how then can we answer interventional questions such as “Does smoking cause cancer?” or even counterfactual ones as “If I had left one minute earlier, would I have managed to arrive on time?” This is the subject of Causal Inference, as pioneered and formalized by Judea Pearl. In my talk, I want to focus on how such problems can be modelled and solved using tools from programming languages theory.
I will aim to give a general introduction to causal inference from a programmer’s point of view. I will then present work-in-progress from an ongoing collaboration dedicated to the extension of a probabilistic programming language to a causal probabilistic programming language; this includes operational semantics, a type system and denotational semantics using graded monads.
- Speaker: Dario Stein (Radboud University)
- Friday 28 March 2025, 14:00-15:00
- Venue: SS03, Computer Laboratory.
- Series: Logic and Semantics Seminar (Computer Laboratory); organiser: Ioannis Markakis.