项目描述

In the 2020s, exoplanet studies are increasingly focussing on planetary chemical composition and its origins in protoplanetary disks. Some of the key goals are to link planetary elemental abundances to their formation location and migration history in a disk, and to establish the origins of habitable chemical compositions. Questions also abound concerning the potential chemical diversity of Earth-like worlds, or the origins and nature of various types of planets such as hot Jupiters or super-Earths. To tackle the above problems, we must study the composition, structure, and processes in planet-forming environments.

We invite PhD applications to work on planet formation science using revolutionary instruments such as the ALMA interferometer or JWST; on the physical-chemical modelling of planet formation processes and environments; and on the connections between planetary systems, their natal disks, and their host stars. You are welcome to contact me to discuss any details.

In my group, we mainly focus on studying protoplanetary disks, using our own observations and models (e.g. Kama et al. 2016; Keyte et al. 2022), but also contributing in large, international ALMA programmes which will provide a wealth of data on protoplanetary disk composition over the next few years. We are also working on projects relating host stars to their disks and planets (see e.g. Jermyn & Kama 2018; Kama et al. 2022), notably EXOHOST, and are heavily involved in the upcoming Ariel mission, which is led from UCL and will characterise the composition of ~1000 planets.

The project will have two components: one on physical-chemical planet formation models, and another on observations of protoplanetary disks, in particular from ALMA or JWST. The balance of these components will be determined in discussion with the applicant. Your aim will be to study chemical tracers of planet formation history, which are increasingly relevant with new exoplanet atmosphere characterisation capabilities from JWST and the upcoming UCL-led Ariel mission. Some background in coding (Python) will be advantageous.

Developing Bio-orthogonal Ynamine Reagents for the Preparation of Next-Generation Antibody-Drug Conjugates

资助博士项目（全球学生）

关于项目

Biomolecule-based therapeutics – or biologics – have emerged as powerful modalities to treat diseases that are typically beyond the reach of conventional small molecules. However, to reach the full potential of biologics to deliver therapeutic payloads to the site of interest, synthetic methods are required to prepare these biologics (e.g., antibodies, therapeutic oligonucleotides). The current state-of-the-art in the preparation of antibody bioconjugates typically involve the formation of product mixtures where the site of functionalisation and the number of functional sites is not defined.

Previous work – Our collaborative team has recently identified the utility of aromatic ynamines as a superior reagent for the site-specific functionalisation of azides via a Cu-catalyzed alkyne-azide cycloaddition (CuAAC) reaction.[1-2] These alkyne surrogates require significantly less Cu catalyst are the only alkyne reagents reported to date which enable chemoselective control in a sequential two-step CuAAC process.[1,3]

Project Objective - The principal objective of this studentship is to develop aromatic ynamines as a powerful new bio-orthogonal reaction platform for the chemoselective tagging of antibodies and therapeutic oligonucleotides.

The specific aims of the project are to:

(i) gain a mechanistic understanding of the enhanced chemoselectivity of ynamines in CuAAC reactions, and potentially across other bio-orthogonal reaction classes.

(ii) establish conditions for chemoselective modification of antibodies and oligonucleotides.

(iii) prepare antibody-oligonucleotide conjugates and explore their biological activity in cell models.

mRNA epigenetics: Charaterization of a novel layer of gene regulation for essential brain functions

For over 40 years we know about modified nucleotides in mRNA, but the functions for these essential modifications are largely elusive. Recent characterization of the FTO (fat mass and obesity associated) gene as a demethylase of N6-methyladenosine (m6A) indicates key roles for mRNA methylation in neuronal control of body weight1. FTO is highly expressed in the brain and has also been associated with other neurological disorders such as depression, epilepsy and Alzheimers disease.

We use a Drosophila genetic model system to investigate the biological function of these modifications2. Our aim is to identify which mRNAs are modified and where in these mRNAs modifications are localised. Furthermore, we aim to characterize the molecular machinery that places these modifications and the signalling pathways that regulate the dynamics of them. Last, we like to know the biological functions for these modifications.