Biology subjects

Lim, H. H.

Publications and source records attributed to Lim, H. H..

4 recordsLinked to original sources

bioRxiv2025

Metabolic engineering approach to boost γ-decalactone production in S. cerevisiae identifies a critical role for the peroxisomal Fatty Acyl-CoA Synthetase Faa2

Lactones constitute a family of aroma compounds found in fruits, flowers and vegetables and are in high demand in the food industry. Previous studies have reported biotransformation of castor beans-extracted ricinoleic acid to {gamma}-decalactone using oleaginous yeast Yarrowia lipolytica. Given the potential toxicities associated with castor beans, we have used a metabolic flux-engineering approach to produce {gamma}-decalactone from oleic acid in Saccharomyces cerevisiae. Intracellular conversion of oleic acid to ricinoleic acid was achieved by the expression of oleate hydroxylase Fah12 from ergot fungus Claviceps purpurea. Glycerol-3-phosphate dehydrogenase-mediated glycerol synthesis was identified as the major metabolic diversion of oleic acid that negatively impacts {gamma}-decalactone yields. Chemogenomic profiling analysis revealed that the tryptophan biosynthetic pathway provides resistance to {gamma}-decalactone-mediated toxicity in yeast. Overexpression of tryptophan transporter Tat1 enhanced {gamma}-decalactone production by about 3- fold. Deficiency of genes encoding the cytoplasmic fatty acyl CoA synthetases FAA1 or FAA4 alone did not significantly influence {gamma}-decalactone production. However, deficiency of peroxisomal FAA2 drastically diminished the yield of {gamma}-decalactone. Thus, this study uncovers the metabolic barriers to oleic acid-to-{gamma}-decalactone conversion and identifies Faa2 as an essential element in this biotransformation.

synthetic biology↗

bioRxiv2020

Noise Invariance in Inferior Colliculus Neurons is Dependant on the Input Noisy Conditions

The auditory system is extremely efficient to extract audio information in the presence of background noise. However, the neural mechanisms related to this efficiency is still greatly misunderstood, especially in the inferior colliculus (IC). In fact, while noise processing under different conditions has been investigated at the auditory cortex level, studies in the IC have been much limited. One interesting observation has been that there seems to be some degree of noise invariance in the IC in the presence of white noise. We wish to broaden this knowledge by investigating if there is a difference in the activity of neurons in the IC, when presenting noisy vocalisations with different types of noises, input signal-to-noise ratios (SNR) and signal levels. We do so using a generalized linear model (GLM), which gives us the ability to study the neural activity under these different conditions at a per neuron level. We found that non-stationary noise is the only noise type that clearly contributes to the neural activity in the IC, regardless of the SNR, input level or vocalisation type. However, when presenting white or natural stationary noises, a great diversity of responses was observed for the different conditions, where the activity of some neurons was affected by the presence of noise and the activity of others was not. Therefore, there seems to be some level of background noise invariance as early as the IC level, as reported before, however, this invariance seems to be highly dependent on the noisy conditions. New & NoteworthyThe neural mechanisms of auditory perception in the presence of background noise are still not well understood, especially in the IC. We studied neural activity in the IC when presenting noisy vocalisations using different background noise types, SNRs and input sound levels. We observed that only the non-stationary noise type clearly contributes to the neural activity in the IC. The noise invariance previously observed in the IC thus seems dependent on the noisy conditions.

neuroscience↗

bioRxiv2018

A multi-scale model of the yeast chromosome-segregation system

In dividing cells, depolymerizing spindle microtubules move chromosomes by pulling at their kinetochores. While kinetochore subcomplexes have been studied extensively in vitro, little is known about their in vivo structure and interactions with microtubules or their response to spindle damage. Here we combine electron cryotomography of serial cryosections with genetic and pharmacological perturbation to study the yeast chromosome-segregation machinery at molecular resolution in vivo. Each kinetochore microtubule has one (rarely, two) Dam1C/DASH outer-kinetochore assemblies.\n\nDam1C/DASH only contacts the flat surface of the microtubule and does so with its flexible \"bridges\". In metaphase, 40% of the Dam1C/DASH assemblies are complete rings; the rest are partial rings. Ring completeness and binding position along the microtubule are sensitive to kinetochore attachment and tension, respectively. Our study supports a model in which each kinetochore must undergo cycles of conformational change to couple microtubule depolymerization to chromosome movement.

cell biology↗

bioRxiv2017

Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway

Ultrasound (US) can noninvasively activate intact brain circuits, making it a promising neuromodulation technique. However, little is known about the underlying mechanism. Here, we apply transcranial US and perform brain mapping studies in guinea pigs using extracellular electrophysiology. We find that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminates the US-induced activity, revealing an indirect auditory mechanism for US neural activation. US likely vibrates the cerebrospinal fluid in the brain, which is continuous with the fluid in the cochlea via cochlear aqueducts; thus, US can activate the ascending auditory pathways and other non-auditory regions through cross-modal projections. This finding of a cochlear fluid-induced vibration mechanism challenges the idea that US can directly activate neurons in the intact brain, suggesting that future US stimulation studies will need to control for this effect to reach reliable conclusions.

neuroscience↗