Honours and Masters project

Recent technological advances in micro and nano-fabrication technology and high-yield electrophysiology techniques allowed us to record the activity of hundreds/thousands of neurons simultaneously. This has spurred renewed interest in applying multi-electrode extracellular electrophysiology approaches in the field of neuroscience. Each electrode samples the activity of one or more neurons in its vicinity.

The aim of this project is to understand the computations underlying animals’ choice in dynamic and changing environments. The natural environment is multisensory, dynamic and changing, requiring animals to continually adapt and update their learned knowledge of statistical regularities in the environment that signal the presence of primary needs like water, food and mates. Yet, how the brain adapts and updates itself to the non-stationary and dynamic attributes of natural environments remains unexplored.

Spontaneous synchronization is a common phenomenon occurring in diverse contexts, from a group of glowing fireflies at night or chirping crickets in a field to a network of coupled neurons in the brain. The study of synchronization helps to understand how uniform behaviors emerge in populations of heterogeneous neurons. At a macroscale level, the cortex operates in two classically-defined states: “synchronized” state which is characterized by strong low-frequency fluctuations and “desynchronized” state in which low-frequency fluctuations are suppressed.

Antimicrobial resistance (AMR) has posed critical challenges to global health. The World Health Organization has identified carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales as the top-priority pathogens urgently to be targeted for the development of novel therapeutic options. Recently, bacteriophage therapy has attracted extensive attention owing to its potential as novel antimicrobials to combat MDR pathogens.

Antimicrobial resistance poses significant medical challenge worldwide. Misuse, overuse or suboptimal dosing of antibiotics are major driving factors of antimicrobial resistance. Pharmacokinetic/pharmacodynamic (PK/PD) modelling is critical for designing optimal antimicrobial therapies to maximise the efficacy and minimise the emergence of resistance. However, conventional PK/PD modelling is generally based on viable counting on agar plates after overnight culture and employs a population approach.

Immune protection provided by immune memory underpins successful vaccines and is mediated mainly by memory lymphocytes and long-lived antibody- secreting cells. In particular, B cell memory is key to providing a rapid and robust response upon secondary infection and continual serum antibody protection. We are working to elucidate the crucial epigenetic mechanisms that generate and maintain B cell memory, and how B cells may retain molecular and functional plasticity under chronic pathogenic pressure.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer, with a high mortality rate. Therapies for PDAC are limited to chemotherapy, which has been ineffective to treat advanced stages of the cancer. Therefore, it is critical to identify biomarkers and develop targeted therapies, to improve early diagnosis and patient care. We have generated mass spectrometry (proteomics and phosphoproteomics) data from 15 PDAC patient-derived xenographs (PDX), which have been grown in mice.

The evolutionary back and forth between hosts and mobile genetic elements drives the innovation of remarkable molecular strategies to sense or conceal foreign genetic material. The Knott Lab uses bioinformatics, biochemistry, and structural biology to understand how CRISPR-Cas and other novel immune systems specifically sense DNA or RNA. We aim to better understand the function of nucleic acid sensors to harness their activity as tools for molecular diagnostics or as innovative biomedicines.

Amphetamine (AMPH) is a widely abused drug, but before it was restricted in use it was an effective weight loss agent. We have shown that a distinct group of neurons controls a large part of the body’s weight loss response to amphetamine. In 2017 a single cell RNA sequencing project was published (Campbell, Macosko et al. 2017) that described transcriptional profiles of 21,000 neurons, amongst which are the neurons we have shown mediate the weight loss caused by amphetamine.

In this project, we aim at surveying relevant computational tools/models used for automatic question generation, and then comparing the effectiveness of these tools/models by using existing datasets.