师说 | 对话生物系Heriberto Vélëz博士：与真菌“交朋友”，17年来他始终坚持这件事……
Please scroll down for the English version
漫步于森林中，你可能会看到形形色色的蘑菇，除了想到蘑菇有毒，你知道这些真菌或可以用于药物研发与癌症治疗吗？
来自温肯生物系的Heriberto Vélëz (Eddy)博士深耕真菌病理性、真菌低温生物学、有复杂核基因组的真菌研究，致力于从真菌中找到抗癌化合物生产的突破口。英语、西班牙语、瑞典语、葡萄牙语、意大利语，精通五国语言的他热爱旅行，探索世界各地森林中的真菌，也热爱学习新的语言，和各地学生交流学习。
本期“师说”对话Dr. Vélëz，聚焦他在植物病理学与生物技术的研究发现，探索他与真菌的科研故事。
关于Heriberto Vélëz，博士
在加入温州肯恩大学之前，Heriberto Vélëz (Eddy)博士是瑞典农业科学大学 (SLU) 的研究科学家，致力于使用真菌粗糙脉孢菌作为模式生物，研究“趋于中介和染色质结构的应激反应的进化保守机制”。他分别于 2000 年和 2006 年毕业于北卡罗来纳州立大学，获得生物化学学士学位和植物病理学与生物技术博士学位。在圣路易斯大学，他担任有机生物学研究学院的负责人，为博士生教授课程、组织研讨会。他的研究方向包括真菌冷冻生物学和具有复杂核基因组的真菌。其中许多真菌会在农业和林业部门引起毁灭性的疾病，而其他真菌正在被研究作为新药、抗生素化合物和生物燃料生产的来源。他目前正在参与加德满都大学（尼泊尔）生物技术系的国际合作，并继续与瑞典农业科学大学（瑞典乌普萨拉）森林真菌学和植物病理学系合作。
与真菌“打交道”的那些年
今年已经是Dr. Vélëz和真菌打交道的第17个年头了。本科时期，偶然的一次生物实验课中，他第一次接触了火炬松内生长素诱导的真菌基因。也是这次实验，让他开始思考真菌与植物之间的共生关系，从此将研究方向转向了真菌病理性的研究。Dr. Vélëz相信：“真菌将是生物技术学科中非常重要的一环。” 在生物技术层面，真菌已被用于制作青霉素、洛伐他汀等医疗药物。为探索更广泛的应用领域，他将目光转向目前医疗界最棘手的难题之一——癌症治疗上。
抗癌化合物紫杉醇 (Taxol)
他与加德满都大学（尼泊尔）的科研团队意外发现，某种真菌能产生一种名叫紫杉醇的抗癌化合物(Taxol)，这种化合物可用于乳腺癌和肺癌等癌症的化疗进程。目前，能产生紫杉醇化合物的树木面临着过度采伐的严峻挑战。因此，Dr. Vélëz希望能从真菌中找到紫杉醇生产的突破口，这也是他想在温肯研究的项目之一。
《喜马拉雅红豆杉内生真菌中紫杉醇和β-微管蛋白的分离》研究论文
此外，Dr. Vélëz注意到生活在寒冷环境中的真菌会产生冰结合蛋白（IBP）以保护它们免受冰冻，而冰结合蛋白在中国市场上的应用颇为广泛，他也想在温肯启动该方面的的研究，助力食品市场中的防冻蛋白、医疗领域中的冷冻手术、农业的防冻技术等应用的发展。
在温州与真菌“再续前缘”
“温州最吸引我的，是连绵不绝的山与森林，在那里，真菌的种类繁多，我可以重新投身于对真菌的研究之中。”来到温肯之前，Dr. Vélëz曾作为科研员在瑞典农业科学大学开展有关真菌的研究。由于团队的资金中断、科研进度停滞不前，他将目光投向了温肯。“中国正在大力投资科研发展，温肯也为科研人员提供了许多激励措施与资金支持。”远渡重洋来到中国后，他决定在温肯教授生物课程，同时完成此前停滞的真菌研究。
在瑞典乌普萨拉森林漫步时观察到的真菌
在瑞典的冬天，Dr. Vélëz每天都会在两点半日落前去森林里观察采集真菌的样本材料，带回实验室中开展后续的研究。而在中国，他发现在气候较为湿热的温州，有着许多在瑞典干冷气候下无法生存的真菌种类，他笑言：“笔架山的树林就像一个巨大的真菌培养皿，我可以在那儿找到瑞典不常见的真菌种类，并对其开展深入研究！”
科研之路挑战重重，也要坚持心之所往
“找到自己所热爱的事，坚持下去做好它，即使会面临一些挑战。”对于Dr. Vélëz来说，将真菌分离到纯培养物的过程绝对是一项不小的挑战。由于森林并不是一个无菌的环境，因此在培养从森林采集的真菌细胞时，需要多次使其增殖分离到纯培养物。在这个过程中，可能还会有培养皿中生长较快的真菌群落覆盖生长较慢的群落，从而无法观测后者的生长情况。
然而，别人眼里枯燥反复的试验，他总能用兴趣的眼光去化解。“我喜欢挑战，喜欢和真菌一起工作！”他这样说道。就是凭借这不懈的热情与坚持，在一次用蓝藻细菌的基因生产生物燃料的实验中，他从实验室使用微流体技术区分酵母产生的特定酶中获得灵感，由此联想到或许也可以用这种微流体来净化和处理真菌。
采集森林中的真菌
目前，微流体技术已在《科学报告》(Scientific Reports) 中发表，但极少用于真菌研究，该项技术可以在几秒钟筛选1000个培养皿，来加快真菌的纯化。Dr. Vélëz了解到，在中国也有多所大学在研究微流体学和纳米流体学，他希望能在明年夏天与这些大学开展合作，继续微流体“净化”真菌的后续研究，将微流体技术整合到担子菌真菌的研究中去。
谈到即将出版的研究课题——巨茶菌中甲基异虫抑素A的代谢途径时，Dr. Vélëz向记者介绍：“我们此前尝试用CRISPR/Cas9 技术将编码甲基特费斯汀生产的其中一个基因删除，但是当涉及到基因操作时，工作常常变得十分艰难。”今后，他计划先提交申请，得到中国植物出入境的审批许可，将实验所需真菌从瑞典运送到中国，继续未完成的研究。
师生搭档科研，尝试新的研究方向
“学生对知识的渴望让我惊叹! 这也是我来到温肯成为一名生物老师的原因。”来到温肯之前，Dr. Vélëz曾在俄罗斯的托木斯克州立大学教授生物科学的相关课程，也正是这段经历坚定了他继续教师事业的决心。他感叹道：“当我在制作真菌培养皿或转移真菌培养物时，学生们也积极地想要尝试参与这个过程，即使这并不是课程的要求。”Dr. Vélëz喜欢探索新的科研课题，了解到真菌产生的一些化合物正在医学上作为抗抑郁药成分进行测试，他也建议温肯主修心理学辅修生物的学生可以从此切入，在真菌与心理治疗的交叉领域中找到研究的新方向。
Dr. Vélëz在温肯
近日，Dr. Vélëz正在指导三名学生关于植物与昆虫的论文写作，与他们探讨创新的研究方向。他认为，研究项目将为学生提供充足的机会来练习和发展他们解决问题的能力、独立性与创造力，他欢迎更多的温肯儿积极参与到科研项目中来，与他一起探索生物的新兴领域。
为了更好地与周围人交流，他也在努力学习中文：“语言代表着我被接纳的第一步，我想要更好地融入温州的文化，融入中国这个国家。”他还希望能在未来的教学中，与温肯儿有更密切的交流，帮助学生们发现自己感兴趣的科研领域，展开新课题的研究合作。
Making friends with fungi, he has been insisting on this for 17 years…
(Interview with Dr. Heriberto Vélëz, Biology, College of Science, Mathematics and Technology at Wenzhou-Kean University)
Wandering in the forest, you may notice fungi of all shapes and colors. Besides the thought that fungi (mushrooms) are poisonous, did you know they can also be used in drug discovery and cancer treatment?
Dr. Heriberto Vélëz (Eddy) from the College of Science, Mathematics and Technology is dedicated to conducting research on the pathology of fungi and finding breakthroughs in producing anticancer compounds from fungi. Fluent in English, Spanish, Swedish, Portuguese, and Italian, Dr. Vélëz loves to travel and explore fungi in forests worldwide. He is also keen on learning new languages and interacting with students all over the world.
This time, we invite Dr. Vélëz to share his discoveries in phytopathology and biotechnology, uncovering the story of his research with fungi.
The years spent with fungi
This is Dr. Vélëz’s 17th year working with fungi. He first got interested in fungi during his junior year at North Carolina State University, (when he was doing his Bachelor's thesis) working with auxin-induced genes in loblolly pine. It was this experiment that led him to think about the symbiotic relationship between fungi and plants. From then on, he shifted his research direction to the study of pathogenic fungi. Dr. Vélëz believes that “Fungi will be a very important part of biotechnology.” At the biotechnological level, fungi have been used to make antibiotics and medical drugs such as penicillin and lovastatin. To explore a wider range of applications, he turned his attention to one of the toughest challenges in medicine today - cancer treatment.
While collaborating with researchers from Kathmandu University (Nepal), he and his team have worked with fungi that can produce paclitaxel, an anti-cancer compound called Taxol, which was isolated from Taxus Wallichiana. This compound can be used during chemotherapy for cancers such as breast and lung cancer. Currently, trees that produce paclitaxel are facing a severe challenge of over-harvesting. Therefore, Dr. Vélëz hopes to find a breakthrough from fungi, which is one of the projects he wants to work on at WKU.
In addition, noting that fungi that live in cold environments produce ice-binding proteins (IBPs) to protect them from freezing, and IBPs are widely used in Chinese markets, Dr. Vélëz is looking forward to initiating research in this area at WKU. Such research can help develop antifreeze proteins in the food industry, cryosurgery in the medical field, antifreeze technology in agriculture, and other areas.
Pick up where he left off
“What attracted me most in Wenzhou were the rolling hills and forests, where various fungi hide, enabling me to get back into my research on fungi.” Before coming to WKU, Dr. Vélëz worked as a Research Scientist, conducting fungal research at the Swedish University of Agricultural Sciences. Due to the interruption of funding and stalled research progress, he began to set his sights on WKU. “Compared with Sweden and most European countries, China is investing heavily in research and development, and WKU also provides many incentives and financial support for researchers.” After traveling all the way to China, he decided to teach Biology at WKU while completing his previous fungal research.
Every winter in Sweden, Dr. Vélëz went to the forest before sunset at half past two, observing and collecting fungal samples, which he brought back to the lab for further study. In China, he found that in Wenzhou, where the climate is relatively hot and humid, many fungal species could not survive in Sweden’s dry and cold climate. He said: "The forest of Bijia Mountain surrounding the WKU campus is like a giant petri dish for fungi, where I can discover fungi species not commonly found in Sweden, thus carrying out in-depth research on them!"
Find your passion and stick to it
“Find what you are passionate about and stick to it until it is well done, even if there are challenges.” For Dr. Vélëz, the process of isolating fungi into pure cultures is definitely a challenge. Since the forest is not a sterile environment, culturing fungal cells collected from the forest requires several times of multiplying and separating. One may also face a challenge where the faster-growing fungal colonies in the petri dish override the slower-growing ones, making it impossible to observe the latter.
However, what others may see as dull and repetitive experiments, he always resolves with interest. “I love challenges and working with fungi!” He said so. It was this relentless enthusiasm and persistence that inspired him with the idea of integrating microfluidics into basidiomycete fungal research. From this inspiration, he associated the idea with the possibility of purifying and treating fungi with microfluidics.
Currently, microfluidics has been published in Scientific Reports but is rarely applied in fungal research. This technology can be used to speed up the purification of fungi by screening 1,000 “petri dishes” or rather 1,000 “microdroplets” in a few seconds. Dr. Vélëz realized that several universities in China are also working on microfluidics and nanofluidics. He hopes to cooperate with these universities next summer, and follow up on the previous research.
When it comes to the forthcoming research, Dr. Vélëz introduced, “I've identified the genes that are encoding the enzymes for methyl-terfestatin production. But there are two enzymes. There are two different pathways that this could go. If I delete one of the genes for one of the enzymes, would that change the pathway? So, it's really difficult to do any kind of genetic work.” In the future, he hopes to continue his research at WKU. He plans to get Chinese approval to enter and exit plants and transport the needed fungi from Sweden to China, continuing the unfinished research.
Trying out new research directions with students
“I am amazed by students’ thirst for knowledge. That's why I came to WKU”. Prior to coming to WKU, Dr. Vélëz taught courses in biological sciences at Tomsk State University in Russia, and it was this experience that solidified his desire to become a teacher. He exclaims, "When I was making media to grow fungi or to transfer fungal cultures, the students actively wanted to try to participate in the process, even if it wasn't a requirement of the course." Dr. Vélëz enjoys exploring new research topics and he suggested to Lin (a WKU psychology student minoring in Biology), to look into some of the compounds produced by fungi that are being medically tested as antidepressants. “Some of these compounds are showing promising results,” he told Lin. “Perhaps Lin will find new ideas for the direction of his own research interests in the intersection of fungi and psychotherapy”.
These days, Dr. Vélëz is co-supervising three students in their research paper on plants and insects, discussing innovative research directions with them. When it comes to his own research, he believes that his research interests will provide ample opportunities for the students to practice and develop their problem-solving skills, independence, and creativity. He welcomes more students from WKU to actively participate in research projects, joining him in exploring emerging areas of biology.
Dr. Vélëz is also adapting his life in Wenzhou. To better communicate with the people around him, he is making efforts to learn Chinese. “Language represents the first step of acceptance. I want to better integrate into the culture of Wenzhou and China," he said with a smile. Aiming to help students discover their own research interests while collaborating on new projects, Dr. Vélëz hopes to have closer interactions with WKU students during his future teaching.
文稿编辑 | 项温蔚
图片｜受访者提供
制作 | 项温蔚
一审 | 叶琼 陈慧
二审 | 王舒
三审 | 吕卓环
责编 | 媒体中心▼
推 / 荐 / 阅 / 读
ChatGPT背后的喜与忧，温肯学者版解读来了！