Biology subjects

Gouveia, P.

Publications and source records attributed to Gouveia, P..

3 recordsLinked to original sources

bioRxiv2024

Zebrafish Avatar-test predicts patient's tumor response to chemotherapy in breast cancer: a co-clinical study towards personalized medicine

Chemotherapy remains the mainstay in most high-risk breast cancer (BC) settings, with several equivalent options of treatment. However, the efficacy of each treatment varies between patients and there is currently no test to determine which option will be the most effective for each individual patient. Here, we developed a fast in-vivo test for BC therapy screening: the zebrafish patient derived xenograft model (zAvatars), where in-vivo results can be obtained in just 10 days. To determine the predictive value of the BC zAvatars we performed a clinical study, where zAvatars were treated with the same therapy as the donor-patient and their response to therapy was compared. Our data shows a 100% correlation between patients clinical response to treatment and its matching zAvatar. Altogether, our results suggest that the zAvatar model constitutes a promising in-vivo assay to optimize cancer treatments in truly personalized manner.

cancer biology↗

bioRxiv2023

Compartmentation of photosynthesis gene expression between mesophyll and bundle sheath cells of C4 maize is dependent on time of day

Compared with the ancestral C3 state, C4 photosynthesis enables higher rates of photosynthesis as well as improved water and nitrogen use efficiencies. In both C3 and C4 plants rates of photosynthesis increase with light intensity and so are maximal around midday. We report that in the absence of light or temperature fluctuations, photosynthesis in maize peaks in the middle of the subjective photoperiod. To investigate molecular processes associated with these changes, we undertook RNA-sequencing of maize mesophyll and bundle sheath strands over a 24-hour time-course. Cell-preferential expression of C4 cycle genes was strongest between six and ten hours after dawn when rates of photosynthesis were highest. For the bundle sheath, DNA motif enrichment and gene co-expression analyses suggested members of the DOF and MADS-domain transcription factor families mediate diurnal fluctuations in C4 gene expression, and trans-activation assays in planta confirmed their ability to activate promoter fragments from bundle sheath expressed genes. The work thus identifies transcriptional regulators as well as peaks in cell-specific C4 gene expression coincident with maximum rates of photosynthesis in the maize leaf at midday.

plant biology↗

bioRxiv2018

Synergistic binding of bHLH transcription factors to the promoter of the maize NADP-ME gene used in C4 photosynthesis is based on an ancient code found in the ancestral C3 state

C4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate a carbon concentrating mechanism that increases photosynthetic efficiency. This specialised form of photosynthesis is particularly common in the PACMAD clade of grasses, and is used by many of the worlds most productive crops. The C4 cycle is accomplished through cell-type specific accumulation of enzymes but cis-elements and transcription factors controlling C4 photosynthesis remain largely unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we aimed to better understand molecular mechanisms associated with the evolution of C4 photosynthesis. Two basic Helix-Loop-Helix (bHLH) transcription factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4 NADP-ME promoter from maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis-elements separated by a seven base pair spacer synergistically bind either ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4 species of the PACMAD clade. Our analysis is consistent with this cis-element pair originating from a single motif present in the ancestral C3 state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory code built on G-box recognition by bHLH to regulate the NADP-ME gene. More broadly, our findings also contribute to the understanding of gene regulatory networks controlling C4 photosynthesis.

plant biology↗