ZIZHUO LU

I am a highly motivated individual with a strong foundation in pharmacology, developed over three years of study and a year of intensive research for my Master’s project at UCL. During this time, I became proficient in the patch-clamp technique and am now working as a research assistant at ShanghaiTech University, where I conduct patch-clamp experiments. I am currently pursuing a PhD in pharmacology or related fields.

MASTER’S RESEARCH PROJECT | Oct 2024 - May 2024

Laboratory of Professors Mark Farrant and Stuart Cull-Candy Department of Neuroscience, Physiology and Pharmacology, UCL

Oct 2023 - Apr 2024

I conducted my Master project: Effects of missense mutations in the TARP-γ2 gene on its regulation of AMPA receptor gating properties in Professors Mark Farrant and Stuart Cull-Candy's Laboratory at University College London. The project involved nine months tense working in the labotory, as well as written a research plan, a dissertation and a face-to-face oral presentation and a question-and-answer session. I got a overall grade of 69.6 in this project.

The α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are tetrameric ionotropic glutamate receptors essential for fast excitatory neurotransmission and synaptic plasticity. Their function is modulated by auxiliary subunits, including the TARP family member γ2 (stargazin), which influences receptor trafficking, gating, pharmacology, and sensitivity to intracellular polyamine block.

The CACNG2 gene encodes the TARP γ2 protein, and a de novo missense mutation, V143L, which weakens the interaction between AMPARs and γ2, has been identified as disease-related, raising the possibility that similar mutations may have similar effects. My Master's project focused on investigating the impact of other de novo mutations found in patients with neurodevelopmental disorders, such as F18L, V112A, and S125R, on the modulatory function of AMPARs.

To do this, I made patch-clamp recordings (outside-out configuration) from HEK293 cells expressing GluA2(Q) alone or GluA2(Q) with either wild-type γ2 (WT γ2) or each of three γ2 variants, and examined three features of AMPARs including channel kinetics, sensitivity to voltage dependent polyamine block, and relative kainate efficacy.

My results indicated that γ2 mutations V112A and S125R enhance γ2's modulation of channel kinetics. In contrast, the F18L mutation has no effect on γ2's regulation of channel kinetics or sensitivity to polyamine block. Preliminary data suggest that F18L may impair γ2's effect on kainate efficacy, but further data are needed to confirm this.

CURE GRIN LONDON CONFERENCE | March 2024

As a participant, my lab mates and I prepared a poster presenting the preliminary results of our MSci projects for the conference, where we explained the regulatory effects of TARP-γ2 on AMPA receptors and the potential impact of TARP-γ2 missense mutations on receptor function. 

By attending this conference, I gained valuable insights into the pathology and treatment of neurodevelopmental disorders caused by mutations in genes encoding ionotropic glutamate receptors, as well as the latest research findings and future directions in the field.

BACHERLOR’S LITERATURE PROJECT | Sept 2022 - Mar 2023

Supervised by Prof Paola Pedarzani

Department of Neuroscience, Physiology and Pharmacology, UCL

Oct 2022 - Apr 2023

In my Advanced Investigative Project in Pharmacology, I investigated how monoamine neurotransmitters modulate potassium currents in the central nervous system, specifically focusing on three K+ currents: the slow afterhyperpolarization current, M-current, and leak potassium current. I found that most monoamine neurotransmitters suppress K+ currents, leading to increased neuronal excitability. However, further studies are needed to clarify the molecular identities of the K+ channels involved in these modulation mechanisms.